ATP

@article{doi101016s0016003243913729,
    author = "Oppermann, R.H.",
    title = "Proteins, amino acids and peptides",
    year = "1943",
    journal = "Journal of the Franklin Institute",
    url = "https://doi.org/10.1016/s0016-0032(43)91372-9",
    doi = "10.1016/s0016-0032(43)91372-9",
    openalex = "W2320600355"
}

Cycloheximide and acetoxy-cycloheximide specifically inhibit protein synthesis in L-cells growing in suspension culture. In extracts of rat liver, the drugs inhibit transfer of amino acid from soluble RNA to polypeptide. Unlike puromycin, these drugs do not accelerate release of nascent polypeptide chains. The drugs have no effect on protein synthesis in extracts of Escherichia coli.

@article{doi101126science14636501474,
    author = "Ennis, Herbert L. and Lubin, Martin",
    title = "Cycloheximide: Aspects of Inhibition of Protein Synthesis in Mammalian Cells",
    year = "1964",
    journal = "Science",
    abstract = "Cycloheximide and acetoxy-cycloheximide specifically inhibit protein synthesis in L-cells growing in suspension culture. In extracts of rat liver, the drugs inhibit transfer of amino acid from soluble RNA to polypeptide. Unlike puromycin, these drugs do not accelerate release of nascent polypeptide chains. The drugs have no effect on protein synthesis in extracts of Escherichia coli.",
    url = "https://doi.org/10.1126/science.146.3650.1474",
    doi = "10.1126/science.146.3650.1474",
    openalex = "W1980224338"
}

@article{crossref1969synthesis,
    title = "Synthesis of peptides and amino acids",
    year = "1969",
    journal = "Ultrasonics",
    url = "https://doi.org/10.1016/0041-624x(69)90649-0",
    doi = "10.1016/0041-624x(69)90649-0",
    number = "3",
    openalex = "W4250036181",
    pages = "155",
    volume = "7"
}

Abstract We have examined the functional relationship in vivo between purine ribonucleoside triphosphate pool size and the rate of the RNA accumulation. Our findings are as follows. The imposition of stringency leads to a roughly 40% drop in the GTP pool which occurs very quickly; it is complete in less than 10 min, and occurs simultaneously with, or just before, the shutoff of RNA accumulation. A somewhat slower 30% drop in the ATP pool was also observed. In a relaxed mutant, there is a momentary shrinkage of both pools, but they quickly return to normal and thereafter expand. The shrinkage of the ATP and GTP pools during stringency cannot be accounted for as a feedback response to blockade of RNA accumulation; when RNA accumulation is blocked directly by uracil starvation, the ATP and GTP pools expand rather than contract. Shrinkage of the purine ribonucleoside triphosphate pools may be sufficient to account for the reduced rate of RNA accumulation during stringency. When the synthesis of ATP and GTP is blocked directly by purine starvation, the rate of RNA accumulation falls drastically with only about a 40% shrinkage of the two pools. Thus net RNA synthesis in vivo is much more sensitive to purine ribonucleoside triphosphate concentration than is RNA polymerase activity in vitro. Shrinkage of the GTP pool alone may be sufficient to account for the response of RNA accumulation to stringency. When GTP synthesis is blocked directly by guanine or guanosine starvation, a moderate decrease in the GTP pool results in a disproportionate reduction in net RNA synthesis. Despite virtually complete inhibition of net RNA synthesis during guanosine starvation, protein synthesis proceeds at about 25% of the normal rate. This suggests that the synthesis and turnover of messenger RNA is much less affected by a moderate decrease in GTP than is the accumulation of stable forms of RNA.

@article{doi101016s0021925818931054,
    author = "Gallant, Jonathan and Harada, B.",
    title = "The Control of Ribonucleic Acid Synthesis in Escherichia coli",
    year = "1969",
    journal = "Journal of Biological Chemistry",
    abstract = "Abstract We have examined the functional relationship in vivo between purine ribonucleoside triphosphate pool size and the rate of the RNA accumulation. Our findings are as follows. The imposition of stringency leads to a roughly 40\% drop in the GTP pool which occurs very quickly; it is complete in less than 10 min, and occurs simultaneously with, or just before, the shutoff of RNA accumulation. A somewhat slower 30\% drop in the ATP pool was also observed. In a relaxed mutant, there is a momentary shrinkage of both pools, but they quickly return to normal and thereafter expand. The shrinkage of the ATP and GTP pools during stringency cannot be accounted for as a feedback response to blockade of RNA accumulation; when RNA accumulation is blocked directly by uracil starvation, the ATP and GTP pools expand rather than contract. Shrinkage of the purine ribonucleoside triphosphate pools may be sufficient to account for the reduced rate of RNA accumulation during stringency. When the synthesis of ATP and GTP is blocked directly by purine starvation, the rate of RNA accumulation falls drastically with only about a 40\% shrinkage of the two pools. Thus net RNA synthesis in vivo is much more sensitive to purine ribonucleoside triphosphate concentration than is RNA polymerase activity in vitro. Shrinkage of the GTP pool alone may be sufficient to account for the response of RNA accumulation to stringency. When GTP synthesis is blocked directly by guanine or guanosine starvation, a moderate decrease in the GTP pool results in a disproportionate reduction in net RNA synthesis. Despite virtually complete inhibition of net RNA synthesis during guanosine starvation, protein synthesis proceeds at about 25\% of the normal rate. This suggests that the synthesis and turnover of messenger RNA is much less affected by a moderate decrease in GTP than is the accumulation of stable forms of RNA.",
    url = "https://doi.org/10.1016/s0021-9258(18)93105-4",
    doi = "10.1016/s0021-9258(18)93105-4",
    openalex = "W1592201898"
}

The solubilities of amino acids, diglycine, and triglycine have been measured in water and aqueous ethanol as well as dioxane solutions. Free energies of transfer of amino acid side chains and backbone peptide units from water to ethanol and dioxane solutions have been calculated from these data. The results show the similarity between the effects of ethanol and dioxane on the stability of those side chains and peptide units. In particular, the free energies of transfer of hydrophobic side chains to 100% ethanol and dioxane are essentially identical, and have been used to establish a hydrophobicity scale for hydrophobic side chains.

@article{doi101016s002192581977210x,
    author = "Nozaki, Yasuhiko and Tanford, Charles",
    title = "The Solubility of Amino Acids and Two Glycine Peptides in Aqueous Ethanol and Dioxane Solutions",
    year = "1971",
    journal = "Journal of Biological Chemistry",
    abstract = "The solubilities of amino acids, diglycine, and triglycine have been measured in water and aqueous ethanol as well as dioxane solutions. Free energies of transfer of amino acid side chains and backbone peptide units from water to ethanol and dioxane solutions have been calculated from these data. The results show the similarity between the effects of ethanol and dioxane on the stability of those side chains and peptide units. In particular, the free energies of transfer of hydrophobic side chains to 100\% ethanol and dioxane are essentially identical, and have been used to establish a hydrophobicity scale for hydrophobic side chains.",
    url = "https://doi.org/10.1016/s0021-9258(19)77210-x",
    doi = "10.1016/s0021-9258(19)77210-x",
    openalex = "W1588000118"
}

@article{doi1010160005278772904807,
    author = "van Venrooij, W.J.W. and Henshaw, Edgar C. and Hirsch, Carl A.",
    title = "Effects of deprival of glucose or individual amino acids on polyribosome distribution and rate of protein synthesis in cultured mammalian cells",
    year = "1972",
    journal = "Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis",
    url = "https://doi.org/10.1016/0005-2787(72)90480-7",
    doi = "10.1016/0005-2787(72)90480-7",
    openalex = "W2028193958",
    references = "doi1010160022283669903209, doi1010160022283670900914, doi101016s0015626466805734, doi101016s0021925818625098, doi101016s0021925818649889, doi101016s0021925818931054, doi101038226607a0, doi101038227913a0, doi101042bj0620315, openalexw1785914557"
}

@phdthesis{junck1973synthesis1,
    author = "Junck, J. R. and Fox, S. W",
    title = "Synthesis of oligonucleotides by proteinoid microspheres acting on ATP",
    year = "1973",
    publisher = "Naturwissenschaften, v. 60, p. 425-427",
    note = "talkorigins\_source = {true}; raw\_reference = {Junck, J. R., and Fox, S. W., 1973, Synthesis of oligonucleotides by proteinoid microspheres acting on ATP: Naturwissenschaften, v. 60, p. 425-427.}"
}

A formula for diference between amino acids combines properties that correlate best with protein residue substitution frequencies: composition, polarity, and molecular volume. Substitution frequencies agree much better with overall chemical difference between exchanging residues than with minimum base changes between their codons. Correlation coefficients show that fixation of mutations between dissimilar amino acids is generally rare.

@article{doi101126science1854154862,
    author = "Grantham, Richard",
    title = "Amino Acid Difference Formula to Help Explain Protein Evolution",
    year = "1974",
    journal = "Science",
    abstract = "A formula for diference between amino acids combines properties that correlate best with protein residue substitution frequencies: composition, polarity, and molecular volume. Substitution frequencies agree much better with overall chemical difference between exchanging residues than with minimum base changes between their codons. Correlation coefficients show that fixation of mutations between dissimilar amino acids is generally rare.",
    url = "https://doi.org/10.1126/science.185.4154.862",
    doi = "10.1126/science.185.4154.862",
    openalex = "W2044573154"
}

@incollection{doi101016b9780080177083500100,
    author = "Munro, Hamish N. and Hübert, Christine and Baliga, B S",
    title = "Regulation of Protein Synthesis in Relation to Amino Acid Supply—A Review**Unpublished experiments reported here by us were supported by the U.S. Public Health Service grants CA 08893–05 and AM 15364–02.",
    year = "1975",
    booktitle = "Elsevier eBooks",
    url = "https://doi.org/10.1016/b978-0-08-017708-3.50010-0",
    doi = "10.1016/b978-0-08-017708-3.50010-0",
    openalex = "W9410359",
    references = "doi1010160005278772904807"
}

@article{nakashima1980synthesis,
    author = "Nakashima, T. and Fox, S. W.",
    title = "Synthesis of peptides from amino acids and ATP with lysine-rich proteinoid",
    year = "1980",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01733146",
    doi = "10.1007/bf01733146",
    number = "4",
    openalex = "W4230509606",
    pages = "363-363",
    volume = "15"
}

@phdthesis{nakashima1980synthesis2,
    author = "Nakashima, T. and Fox, S. W",
    title = "Synthesis of peptides from amino acids and ATP with lysine-rich protenoid",
    year = "1980",
    publisher = "Journal of Molecular Evolution, v. 15, p. 161-168",
    note = "talkorigins\_source = {true}; raw\_reference = {Nakashima, T., and Fox, S. W., 1980, Synthesis of peptides from amino acids and ATP with lysine-rich protenoid: Journal of Molecular Evolution, v. 15, p. 161-168.}"
}

@article{nakashima1981formation,
    author = "Nakashima, Tadayoshi and Fox, Sidney W.",
    title = "Formation of peptides from amino acids by single or multiple additions of ATP to suspensions of nucleoproteinoid microparticles",
    year = "1981",
    journal = "Biosystems",
    url = "https://doi.org/10.1016/0303-2647(81)90064-2",
    doi = "10.1016/0303-2647(81)90064-2",
    number = "2",
    openalex = "W1965193662",
    pages = "151-161",
    volume = "14",
    references = "doi101007bf00405480, doi101007bf00927027, doi101007bf01734482, doi1010160303264780900131, doi101016c20090031365, doi101016s0047248478800529, doi101021ja01499a069, doi101038282189a0, openalexw2282054059, openalexw3038835020"
}

@misc{nakashima1981formulation3,
    author = "Nakashima, T. and Fox, S. W",
    title = "Formulation of peptides by single or multiple additions of ATP to suspensions of nucleoproteinoid microparticles",
    year = "1981",
    howpublished = "BioSystems, v. 14, p. 151- 161",
    note = "talkorigins\_source = {true}; raw\_reference = {Nakashima, T., and Fox, S. W., 1981, Formulation of peptides by single or multiple additions of ATP to suspensions of nucleoproteinoid microparticles: BioSystems, v. 14, p. 151- 161.}"
}

@incollection{mazur1983synthesis,
    author = "Mazur, Robert H. and Pilipauskas, Daniel R.",
    title = "Synthesis of Dehydro Amino Acids and Peptides",
    year = "1983",
    booktitle = "Prague, Czechoslovakia, August 29–September 3, 1982",
    url = "https://doi.org/10.1515/9783111694344-063",
    doi = "10.1515/9783111694344-063",
    openalex = "W3131530462",
    pages = "319-322"
}

We recently reported that the translational control of protein synthesis by glucose 6-phosphate in gel-filtered, rabbit reticulocyte lysate is exerted on the activity of eukaryotic initiation factor (eIF)-2B, the factor that catalyzes the exchange of GTP for GDP bound to eIF-2, by a mechanism that is independent of the phosphorylation of eIF-2 (alpha subunit). We now demonstrate that two other conditions regulate the activity of eIF-2B in rabbit reticulocyte lysate: polyamines (spermidine and spermine) and amino acid deficiency. In the absence of added polyamines, protein synthesis in gel-filtered lysate is reduced to about 70% and eIF-2B activity to about 35% of optimal. The former is likely a result of the latter, since we find that reticulocyte lysate has about twice the eIF-2B necessary to recycle the eIF-2.GDP generated under conditions of optimal protein synthesis. In contrast, the reduction in eIF-2B activity (to about 50% of optimal) occurring in the absence of added amino acids in unfractionated or gel-filtered lysate is insufficient, by itself, to slow the rate of protein synthesis, and the inhibition of protein synthesis that does occur with amino acid deficiency is exerted on polypeptide chain elongation, not initiation. The reduction in eIF-2B activity occurring with amino acid deficiency cannot be reversed by adding more glucose 6-phosphate or polyamines nor can the reduced eIF-2B activity seen with polyamine deficiency be overcome by increasing the glucose 6-phosphate, suggesting that these three components regulate eIF-2B activity by different mechanisms.

@article{doi101016s0021925820882660,
    author = "Gross, Martin and Rubino, Mark",
    title = "Regulation of Eukaryotic Initiation Factor-2B Activity by Polyamines and Amino Acid Starvation in Rabbit Reticulocyte Lysate",
    year = "1989",
    journal = "Journal of Biological Chemistry",
    abstract = "We recently reported that the translational control of protein synthesis by glucose 6-phosphate in gel-filtered, rabbit reticulocyte lysate is exerted on the activity of eukaryotic initiation factor (eIF)-2B, the factor that catalyzes the exchange of GTP for GDP bound to eIF-2, by a mechanism that is independent of the phosphorylation of eIF-2 (alpha subunit). We now demonstrate that two other conditions regulate the activity of eIF-2B in rabbit reticulocyte lysate: polyamines (spermidine and spermine) and amino acid deficiency. In the absence of added polyamines, protein synthesis in gel-filtered lysate is reduced to about 70\% and eIF-2B activity to about 35\% of optimal. The former is likely a result of the latter, since we find that reticulocyte lysate has about twice the eIF-2B necessary to recycle the eIF-2.GDP generated under conditions of optimal protein synthesis. In contrast, the reduction in eIF-2B activity (to about 50\% of optimal) occurring in the absence of added amino acids in unfractionated or gel-filtered lysate is insufficient, by itself, to slow the rate of protein synthesis, and the inhibition of protein synthesis that does occur with amino acid deficiency is exerted on polypeptide chain elongation, not initiation. The reduction in eIF-2B activity occurring with amino acid deficiency cannot be reversed by adding more glucose 6-phosphate or polyamines nor can the reduced eIF-2B activity seen with polyamine deficiency be overcome by increasing the glucose 6-phosphate, suggesting that these three components regulate eIF-2B activity by different mechanisms.",
    url = "https://doi.org/10.1016/s0021-9258(20)88266-0",
    doi = "10.1016/s0021-9258(20)88266-0",
    openalex = "W1511858736",
    references = "doi1010160005278772904807"
}

A method to correlate the uninterpreted tandem mass spectra of peptides produced under low energy (10-50 eV) collision conditions with amino acid sequences in the Genpept database has been developed. In this method the protein database is searched to identify linear amino acid sequences within a mass tolerance of ±1 u of the precursor ion molecular weight A cross-correlation function is then used to provide a measurement of similarity between the mass-to-charge ratios for the fragment ions predicted from amino acid sequences obtained from the database and the fragment ions observed in the tandem mass spectrum. In general, a difference greater than 0.1 between the normalized cross-correlation functions of the first- and second-ranked search results indicates a successful match between sequence and spectrum. Searches of species-specific protein databases with tandem mass spectra acquired from peptides obtained from the enzymatically digested total proteins of E. coli and S. cerevisiae cells allowed matching of the spectra to amino acid sequences within proteins of these organisms. The approach described in this manuscript provides a convenient method to interpret tandem mass spectra with known sequences in a protein database.

@article{doi1010161044030594800162,
    author = "Eng, Jimmy K. and McCormack, Ashley L. and Yates, John R.",
    title = "An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database",
    year = "1994",
    journal = "Journal of the American Society for Mass Spectrometry",
    abstract = "A method to correlate the uninterpreted tandem mass spectra of peptides produced under low energy (10-50 eV) collision conditions with amino acid sequences in the Genpept database has been developed. In this method the protein database is searched to identify linear amino acid sequences within a mass tolerance of ±1 u of the precursor ion molecular weight A cross-correlation function is then used to provide a measurement of similarity between the mass-to-charge ratios for the fragment ions predicted from amino acid sequences obtained from the database and the fragment ions observed in the tandem mass spectrum. In general, a difference greater than 0.1 between the normalized cross-correlation functions of the first- and second-ranked search results indicates a successful match between sequence and spectrum. Searches of species-specific protein databases with tandem mass spectra acquired from peptides obtained from the enzymatically digested total proteins of E. coli and S. cerevisiae cells allowed matching of the spectra to amino acid sequences within proteins of these organisms. The approach described in this manuscript provides a convenient method to interpret tandem mass spectra with known sequences in a protein database.",
    url = "https://doi.org/10.1016/1044-0305(94)80016-2",
    doi = "10.1016/1044-0305(94)80016-2",
    openalex = "W2026465178",
    references = "doi101126science2675315, openalexw2282054059"
}

In experiments modeling volcanic or hydrothermal settings amino acids were converted into their peptides by use of coprecipitated (Ni,Fe)S and CO in conjunction with H2S (or CH3SH) as a catalyst and condensation agent at 100 degreesC and pH 7 to 10 under anaerobic, aqueous conditions. These results demonstrate that amino acids can be activated under geochemically relevant conditions. They support a thermophilic origin of life and an early appearance of peptides in the evolution of a primordial metabolism.

@article{doi101126science2815377670,
    author = "Huber, Claudia and Wächtershäuser, Günter",
    title = "Peptides by Activation of Amino Acids with CO on (Ni,Fe)S Surfaces: Implications for the Origin of Life",
    year = "1998",
    journal = "Science",
    abstract = "In experiments modeling volcanic or hydrothermal settings amino acids were converted into their peptides by use of coprecipitated (Ni,Fe)S and CO in conjunction with H2S (or CH3SH) as a catalyst and condensation agent at 100 degreesC and pH 7 to 10 under anaerobic, aqueous conditions. These results demonstrate that amino acids can be activated under geochemically relevant conditions. They support a thermophilic origin of life and an early appearance of peptides in the evolution of a primordial metabolism.",
    url = "https://doi.org/10.1126/science.281.5377.670",
    doi = "10.1126/science.281.5377.670",
    openalex = "W2166068250",
    references = "doi101016s0047248478800529"
}

The cyclic depsipeptide phomalide [cyclo(Val-(E)-Aba-Hpp-Hmp-(R)-Leu); Aba = 2-amino-2-butenoic acid, Hpp = (2S)-2-hydroxy-3-phenylpropanoic acid, Hmp = (2S)-2-hydroxy-4-methylpentanoic acid] is the host-selective phytotoxin produced by the fungus [Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode ex Fr.) Desm.] which causes blackleg disease (a devastating disease of several economically important brassica crops). Efficient total syntheses of phomalide, its (Z)-isomer isophomalide, and the two dihydro analogues [(R)-dihydrophomalide and (S)-dihydrophomalide] are described. A [2 + 3] fragment coupling of Cbz-Val-(Z)-Aba with Hpp-Hmp-D-Leu-OBn followed by deprotection and cyclization gave isophomalide which was diastereoselectively isomerized to phomalide by conjugate addition of PhSeH followed by elimination of the corresponding selenoxide. The dihydro analogues were prepared similarly using Cbz-Val-(R)-Abu or Cbz-Val-(S)-Abu (Abu = 2-aminobutanoic acid) in place of Cbz-Val-(Z)-Aba. Biological evaluations of phomalide, isophomalide, and the dihydrophomalides revealed that only phomalide (10(-)(5) M) caused necrotic, chlorotic, and reddish lesions on canola (Brassica napus and Brassica rapa; susceptible to blackleg) leaves whereas no damage was observed on brown mustard (Brassica juncea; resistant to blackleg) or white mustard (Sinapis alba; resistant to blackleg) leaves, even at significantly higher concentrations (10(-)(4) M). Thus, both the presence and configuration of the double bond is crucial for selective phytotoxicity. This is the first reported synthesis of an (E)-Aba-containing natural product, and importantly, the (Z) --> (E) isomerization approach should be applicable to other (depsi)peptide targets thereby allowing investigation of the effect of the double-bond configuration on various properties.

@article{doi101021jo982376p,
    author = "Ward, Dale E. and Vázquez, Alfredo Macías and Pedras, M. Soledade C.",
    title = "Probing Host-Selective Phytotoxicity: Synthesis and Biological Activity of Phomalide, Isophomalide, and Dihydrophomalide",
    year = "1999",
    journal = "The Journal of Organic Chemistry",
    abstract = "The cyclic depsipeptide phomalide [cyclo(Val-(E)-Aba-Hpp-Hmp-(R)-Leu); Aba = 2-amino-2-butenoic acid, Hpp = (2S)-2-hydroxy-3-phenylpropanoic acid, Hmp = (2S)-2-hydroxy-4-methylpentanoic acid] is the host-selective phytotoxin produced by the fungus [Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode ex Fr.) Desm.] which causes blackleg disease (a devastating disease of several economically important brassica crops). Efficient total syntheses of phomalide, its (Z)-isomer isophomalide, and the two dihydro analogues [(R)-dihydrophomalide and (S)-dihydrophomalide] are described. A [2 + 3] fragment coupling of Cbz-Val-(Z)-Aba with Hpp-Hmp-D-Leu-OBn followed by deprotection and cyclization gave isophomalide which was diastereoselectively isomerized to phomalide by conjugate addition of PhSeH followed by elimination of the corresponding selenoxide. The dihydro analogues were prepared similarly using Cbz-Val-(R)-Abu or Cbz-Val-(S)-Abu (Abu = 2-aminobutanoic acid) in place of Cbz-Val-(Z)-Aba. Biological evaluations of phomalide, isophomalide, and the dihydrophomalides revealed that only phomalide (10(-)(5) M) caused necrotic, chlorotic, and reddish lesions on canola (Brassica napus and Brassica rapa; susceptible to blackleg) leaves whereas no damage was observed on brown mustard (Brassica juncea; resistant to blackleg) or white mustard (Sinapis alba; resistant to blackleg) leaves, even at significantly higher concentrations (10(-)(4) M). Thus, both the presence and configuration of the double bond is crucial for selective phytotoxicity. This is the first reported synthesis of an (E)-Aba-containing natural product, and importantly, the (Z) --> (E) isomerization approach should be applicable to other (depsi)peptide targets thereby allowing investigation of the effect of the double-bond configuration on various properties.",
    url = "https://doi.org/10.1021/jo982376p",
    doi = "10.1021/jo982376p",
    openalex = "W2027670418",
    references = "mazur1983synthesis"
}

Almost all discussions of prebiotic chemistry assume that amino acids, nucleotides, and possibly other monomers were first formed on the Earth or brought to it in comets and meteorites, and then condensed nonenzymatically to form oligomeric products. However, attempts to demonstrate plausibly prebiotic polymerization reactions have met with limited success. We show that carbonyl sulfide (COS), a simple volcanic gas, brings about the formation of peptides from amino acids under mild conditions in aqueous solution. Depending on the reaction conditions and additives used, exposure of alpha-amino acids to COS generates peptides in yields of up to 80% in minutes to hours at room temperature.

@article{doi101126science1102722,
    author = "Leman, Luke J. and Orgel, Leslie E. and Ghadiri, M. Reza",
    title = "Carbonyl Sulfide-Mediated Prebiotic Formation of Peptides",
    year = "2004",
    journal = "Science",
    abstract = "Almost all discussions of prebiotic chemistry assume that amino acids, nucleotides, and possibly other monomers were first formed on the Earth or brought to it in comets and meteorites, and then condensed nonenzymatically to form oligomeric products. However, attempts to demonstrate plausibly prebiotic polymerization reactions have met with limited success. We show that carbonyl sulfide (COS), a simple volcanic gas, brings about the formation of peptides from amino acids under mild conditions in aqueous solution. Depending on the reaction conditions and additives used, exposure of alpha-amino acids to COS generates peptides in yields of up to 80\% in minutes to hours at room temperature.",
    url = "https://doi.org/10.1126/science.1102722",
    doi = "10.1126/science.1102722",
    openalex = "W2165194928"
}

Poly(aspartic acid) (PAA) being biodegradable is suitable for various industrial medical and agricultural applications to replace many non‐biodegradable polymers in use. Poly(aspartic acid) can be synthesized by different methods with and without catalyst in different forms such as polysuccinimide, either hydrolyzed to acid or salt. The polymer of (aspartic acid) is present in different forms such as α,β and L, D isomers. The conformational analysis of poly(aspartic acid) was done by various analytical methods. Different combinations of these two isomer present in different percentage can be detected by various methods such as Hoffman degradation, IR, and NMR spectroscopic analysis. From the standard test for biodegradability, it was shown that the polymer is fully biodegradable. In this review, synthesis and characterization of homo and copolymer derivatives of PAA, along with the application and biodegradability in comparison with the other polymer in use, is discussed briefly.

@article{doi10108010601320500189604,
    author = "Thombre, Sunita M. and Sarwade, Bhimrao D.",
    title = "Synthesis and Biodegradability of Polyaspartic Acid: A Critical Review",
    year = "2005",
    journal = "Journal of Macromolecular Science Part A",
    abstract = "Poly(aspartic acid) (PAA) being biodegradable is suitable for various industrial medical and agricultural applications to replace many non‐biodegradable polymers in use. Poly(aspartic acid) can be synthesized by different methods with and without catalyst in different forms such as polysuccinimide, either hydrolyzed to acid or salt. The polymer of (aspartic acid) is present in different forms such as α,β and L, D isomers. The conformational analysis of poly(aspartic acid) was done by various analytical methods. Different combinations of these two isomer present in different percentage can be detected by various methods such as Hoffman degradation, IR, and NMR spectroscopic analysis. From the standard test for biodegradability, it was shown that the polymer is fully biodegradable. In this review, synthesis and characterization of homo and copolymer derivatives of PAA, along with the application and biodegradability in comparison with the other polymer in use, is discussed briefly.",
    url = "https://doi.org/10.1080/10601320500189604",
    doi = "10.1080/10601320500189604",
    openalex = "W2017931181",
    references = "doi101021ja01499a069, doi101021ja01544a027, doi101021ja01546a042"
}

Aminoacyl-tRNA synthetases catalyze the attachment of cognate amino acids to specific tRNA molecules. To prevent potential errors in protein synthesis caused by misactivation of noncognate amino acids, some synthetases have evolved editing mechanisms to hydrolyze misactivated amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing). In the case of post-transfer editing, synthetases employ a separate editing domain that is distinct from the site of amino acid activation, and the mechanism is believed to involve shuttling of the flexible CCA-3' end of the tRNA from the synthetic active site to the site of hydrolysis. The mechanism of pre-transfer editing is less well understood, and in most cases, the exact site of pre-transfer editing has not been conclusively identified. Here, we probe the pre-transfer editing activity of class II prolyl-tRNA synthetases from five species representing all three kingdoms of life. To locate the site of pre-transfer editing, truncation mutants were constructed by deleting the insertion domain characteristic of bacterial prolyl-tRNA synthetase species, which is the site of post-transfer editing, or the N- or C-terminal extension domains of eukaryotic and archaeal enzymes. In addition, the pre-transfer editing mechanism of Escherichia coli prolyl-tRNA synthetase was probed in detail. These studies show that a separate editing domain is not required for pre-transfer editing by prolyl-tRNA synthetase. The aminoacylation active site plays a significant role in preserving the fidelity of translation by acting as a filter that selectively releases non-cognate adenylates into solution, while protecting the cognate adenylate from hydrolysis.

@article{doi101074jbcm605856200,
    author = "Hati, Sanchita and Ziervogel, Brigitte and Sternjohn, Julius and Wong, Fai-Chu and Nagan, Maria C and Rosen, Abbey E and Siliciano, Paul G and Chihade, Joseph W and Musier-Forsyth, Karin",
    title = {Pre-transfer editing by class II prolyl-tRNA synthetase: role of aminoacylation active site in "selective release" of noncognate amino acids.},
    year = "2006",
    journal = "The Journal of biological chemistry",
    abstract = "Aminoacyl-tRNA synthetases catalyze the attachment of cognate amino acids to specific tRNA molecules. To prevent potential errors in protein synthesis caused by misactivation of noncognate amino acids, some synthetases have evolved editing mechanisms to hydrolyze misactivated amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing). In the case of post-transfer editing, synthetases employ a separate editing domain that is distinct from the site of amino acid activation, and the mechanism is believed to involve shuttling of the flexible CCA-3' end of the tRNA from the synthetic active site to the site of hydrolysis. The mechanism of pre-transfer editing is less well understood, and in most cases, the exact site of pre-transfer editing has not been conclusively identified. Here, we probe the pre-transfer editing activity of class II prolyl-tRNA synthetases from five species representing all three kingdoms of life. To locate the site of pre-transfer editing, truncation mutants were constructed by deleting the insertion domain characteristic of bacterial prolyl-tRNA synthetase species, which is the site of post-transfer editing, or the N- or C-terminal extension domains of eukaryotic and archaeal enzymes. In addition, the pre-transfer editing mechanism of Escherichia coli prolyl-tRNA synthetase was probed in detail. These studies show that a separate editing domain is not required for pre-transfer editing by prolyl-tRNA synthetase. The aminoacylation active site plays a significant role in preserving the fidelity of translation by acting as a filter that selectively releases non-cognate adenylates into solution, while protecting the cognate adenylate from hydrolysis.",
    url = "https://pubmed.ncbi.nlm.nih.gov/16864571/",
    doi = "10.1074/jbc.M605856200",
    openalex = "W2063309485",
    pmid = "16864571",
    references = "doi101016s0021925818968419, doi101016s0092867400001823, doi101016s0092867400807461, doi101016s1097276503000984, doi101038347203a0, doi101073pnas494517, doi101073pnas71104135, doi101126science2805363578, doi101126science28554301074, doi101126science7530860"
}

@misc{crossref2007fungicides,
    title = "Fungicides Acting on Amino Acids and Protein Synthesis",
    year = "2007",
    booktitle = "Modern Crop Protection Compounds",
    url = "https://doi.org/10.1002/9783527619580.ch14",
    doi = "10.1002/9783527619580.ch14",
    openalex = "W2484495979",
    pages = "539-560",
    references = "doi1010160732889386900441, doi101016c20130036511, doi101016s0261219499000745, doi101094pd750287, doi101126science14636501474, doi101128mr5711381631993, doi101146annurevmi25100171002415, doi101146annurevphyto40120301093927, doi103181003797275514461, doi105860choice410673"
}

Translating the 4-letter code of RNA into the 22-letter alphabet of proteins is a central feature of cellular life. The fidelity with which mRNA is translated during protein synthesis is determined by two factors: the availability of aminoacyl-tRNAs composed of cognate amino acid:tRNA pairs and the accurate selection of aminoacyl-tRNAs on the ribosome. The role of aminoacyl-tRNA synthetases in translation is to define the genetic code by accurately pairing cognate tRNAs with their corresponding amino acids. Synthetases achieve the amino acid substrate specificity necessary to keep errors in translation to an acceptable level in two ways: preferential binding of the cognate amino acid and selective editing of near-cognate amino acids. Editing significantly decreases the frequency of errors and is important for translational quality control, and many details of the various editing mechanisms and their effect on different cellular systems are now starting to emerge.

@article{doi101146annurevmicro091208073210,
    author = "Ling, Jiqiang and Reynolds, Noah M. and Ibba, Michael",
    title = "Aminoacyl-tRNA Synthesis and Translational Quality Control",
    year = "2009",
    journal = "Annual Review of Microbiology",
    abstract = "Translating the 4-letter code of RNA into the 22-letter alphabet of proteins is a central feature of cellular life. The fidelity with which mRNA is translated during protein synthesis is determined by two factors: the availability of aminoacyl-tRNAs composed of cognate amino acid:tRNA pairs and the accurate selection of aminoacyl-tRNAs on the ribosome. The role of aminoacyl-tRNA synthetases in translation is to define the genetic code by accurately pairing cognate tRNAs with their corresponding amino acids. Synthetases achieve the amino acid substrate specificity necessary to keep errors in translation to an acceptable level in two ways: preferential binding of the cognate amino acid and selective editing of near-cognate amino acids. Editing significantly decreases the frequency of errors and is important for translational quality control, and many details of the various editing mechanisms and their effect on different cellular systems are now starting to emerge.",
    url = "https://doi.org/10.1146/annurev.micro.091208.073210",
    doi = "10.1146/annurev.micro.091208.073210",
    openalex = "W2147488317",
    references = "doi101074jbcm605856200"
}

@misc{buchenauer2011fungicides,
    author = "Buchenauer, Heinrich and Walker, Frank and Gisi, Ulrich and Müller, Urs",
    title = "Fungicides Acting on Amino Acids and Protein Synthesis",
    year = "2011",
    booktitle = "Modern Crop Protection Compounds",
    url = "https://doi.org/10.1002/9783527644179.ch16",
    doi = "10.1002/9783527644179.ch16",
    openalex = "W1564701801",
    pages = "693-714",
    references = "doi1010160732889386900441, doi101016s0261219499000745, doi101094pd750287, doi101126science14636501474, doi101128mr5711381631993, doi101146annurevmi25100171002415, doi101146annurevphyto40120301093927, doi103181003797275514461, doi105860choice410673, openalexw2992285622"
}

Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (i.e. glycine, arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution.

@misc{doi1026434chemrxiv6972785,
    author = "Suárez-Marina, Irene and Turk-MacLeod, Rebecca and Abul‐Haija, Yousef M. and Gromski, Piotr S. and Cooper, Geoffrey M. and Cronin, Leroy",
    title = "Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids",
    year = "2018",
    booktitle = "ChemRxiv",
    abstract = "Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (i.e. glycine, arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution.",
    url = "https://doi.org/10.26434/chemrxiv.6972785",
    doi = "10.26434/chemrxiv.6972785",
    openalex = "W4240956472",
    references = "doi101016jcelrep201512015, doi101016jchembiol201303012, doi101021cr2004844, doi101021jo062586z, doi101038nature08013, doi101038ncomms11328, doi101038ncomms9385, doi101126science1102722, doi101126science1174577, doi101126scienceaad2808, nakashima1980synthesis"
}

Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (i.e. glycine, arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution.

@misc{doi1026434chemrxiv6972785v1,
    author = "Suárez-Marina, Irene and Turk-MacLeod, Rebecca and Abul‐Haija, Yousef M. and Gromski, Piotr S. and Cooper, Geoffrey M. and Cronin, Leroy",
    title = "Integrated Synthesis of Nucleotide and Nucleosides Directed by Amino Acids",
    year = "2018",
    booktitle = "ChemRxiv",
    abstract = "Research on the origin of nucleic acids and proteins has been approached by either multi-step synthesis or simple one-pot reactions, but exploration of their prebiotic chemistry is normally done separately. However, if nucleotides and amino acids co-existed on early Earth, their mutual interactions and reactivity should be considered in exploring the emergence of complex chemical systems that can ultimately evolve. To explore this idea, we set out to investigate nucleotide/nucleoside formation by a simple dehydration reaction of the constituent building blocks (sugar, phosphate, and nucleobase) in the presence of amino acids (i.e. glycine, arginine, glutamic acid, threonine, methionine, phenylalanine and tryptophan). Herein, we report the first example of simultaneous formation of glycosidic bonds between ribose, purines, and pyrimidines under mild conditions without a catalyst or activated reagents, as well as nucleobase exchange. We observed not only the simultaneous formation of nucleotide and nucleoside isomers from several nucleobases, but also the selection of distribution of glycosylation products when glycine was present. This work shows how reaction networks of nucleotides and amino acids should be considered when exploring the emergence of catalytic networks in the context of molecular evolution.",
    url = "https://doi.org/10.26434/chemrxiv.6972785.v1",
    doi = "10.26434/chemrxiv.6972785.v1",
    openalex = "W4254625127",
    references = "doi101016jcelrep201512015, doi101016jchembiol201303012, doi101021cr2004844, doi101021jo062586z, doi101038nature08013, doi101038ncomms11328, doi101038ncomms9385, doi101126science1102722, doi101126science1174577, doi101126scienceaad2808, nakashima1980synthesis"
}

@misc{crossref2019fungicides,
    title = "Fungicides Acting on Amino Acids and Protein Synthesis",
    year = "2019",
    booktitle = "Modern Crop Protection Compounds",
    url = "https://doi.org/10.1002/9783527699261.ch16",
    doi = "10.1002/9783527699261.ch16",
    openalex = "W4238007333",
    pages = "749-759",
    references = "doi101002chem200801831, doi101002ps3506, doi1010079783319233710, doi101016s0261219499000745, doi101094pdis09130970re, doi101094phyto9820205, doi101111mpp12384, doi101128aem0265512, doi103389fmicb201702361, doi105860choice410673"
}

The fundamental roles that peptides and proteins play in today's biology makes it almost indisputable that peptides were key players in the origin of life. Insofar as it is appropriate to extrapolate back from extant biology to the prebiotic world, one must acknowledge the critical importance that interconnected molecular networks, likely with peptides as key components, would have played in life's origin. In this review, we summarize chemical processes involving peptides that could have contributed to early chemical evolution, with an emphasis on molecular interactions between peptides and other classes of organic molecules. We first summarize mechanisms by which amino acids and similar building blocks could have been produced and elaborated into proto-peptides. Next, non-covalent interactions of peptides with other peptides as well as with nucleic acids, lipids, carbohydrates, metal ions, and aromatic molecules are discussed in relation to the possible roles of such interactions in chemical evolution of structure and function. Finally, we describe research involving structural alternatives to peptides and covalent adducts between amino acids/peptides and other classes of molecules. We propose that ample future breakthroughs in origin-of-life chemistry will stem from investigations of interconnected chemical systems in which synergistic interactions between different classes of molecules emerge.

@article{doi101021acschemrev9b00664,
    author = "Frenkel‐Pinter, Moran and Samanta, Mousumi and Ashkenasy, Gonen and Leman, Luke J.",
    title = "Prebiotic Peptides: Molecular Hubs in the Origin of Life",
    year = "2020",
    journal = "Chemical Reviews",
    abstract = "The fundamental roles that peptides and proteins play in today's biology makes it almost indisputable that peptides were key players in the origin of life. Insofar as it is appropriate to extrapolate back from extant biology to the prebiotic world, one must acknowledge the critical importance that interconnected molecular networks, likely with peptides as key components, would have played in life's origin. In this review, we summarize chemical processes involving peptides that could have contributed to early chemical evolution, with an emphasis on molecular interactions between peptides and other classes of organic molecules. We first summarize mechanisms by which amino acids and similar building blocks could have been produced and elaborated into proto-peptides. Next, non-covalent interactions of peptides with other peptides as well as with nucleic acids, lipids, carbohydrates, metal ions, and aromatic molecules are discussed in relation to the possible roles of such interactions in chemical evolution of structure and function. Finally, we describe research involving structural alternatives to peptides and covalent adducts between amino acids/peptides and other classes of molecules. We propose that ample future breakthroughs in origin-of-life chemistry will stem from investigations of interconnected chemical systems in which synergistic interactions between different classes of molecules emerge.",
    url = "https://doi.org/10.1021/acs.chemrev.9b00664",
    doi = "10.1021/acs.chemrev.9b00664",
    openalex = "W3008483803",
    references = "doi101002anie201208397, doi101007pl00006565, doi101021cr2004844, doi101021ja01499a069, doi101038nchem2878, doi101038s415700160012, doi101073pnas9784112, doi101098rsob130156, doi101101cshperspecta034801, doi101126science1161527, doi1011861759220832, fox1958thermal"
}

Heat shock proteins of the 70-kDa family (Hsp70s) are highly abundant and conserved molecular chaperones that help preserve proteostasis primarily by facilitating proper protein folding. Heat shock protein of the 110-kDa family (Hsp110s), a specialized branch of the Hsp70/Hsp110 superfamily, function both as nucleotide exchange factor (NEF) cochaperones for Hsp70s and as independent "holdase" chaperones that stabilize non-native polypeptides to prevent aggregation and facilitate downstream refolding by Hsp70s. While Hsp110 NEF activity is well characterized, the consequences of adenosine 5'-triphosphate (ATP) binding for Hsp110 holdase behavior have remained largely unexplored. Although holdase activity is generally considered nucleotide-independent, reports of ATP-dependent effects have raised questions about the underlying mechanism. Here, we examined the biochemical properties of Multicopy Suppressor of ira1 3 (Msi3), the sole Hsp110 in Candida albicans, to dissect the role of ATP in holdase function. We first identified an inhibitory effect of elevated Mg2+ concentrations on Msi3 holdase activity. This inhibitory effect is counteracted by the intrinsically disordered C-terminal segment, revealing a distinct stabilization role for this region, previously of unknown function. In addition, ATP alleviates inhibition by elevated Mg2+, providing an explanation for an apparent ATP-dependence observed previously. Interestingly, although dispensable for aggregation suppression, ATP modulates Msi3 holdase activity for refolding competence by broadening the concentration range over which it remains productive. Increasing Msi3 concentration improved overall downstream refolding recovery but slowed refolding kinetics, and ATP alleviated this kinetic constraint. Analyses of Hsp105, the major human Hsp110, suggest that these biochemical properties are largely conserved. Together, these findings suggest that ATP modulates Hsp110 holdase activity by tuning the balance between substrate sequestration and engagement dynamics, revealing an ATP-dependent regulatory dimension of Hsp110 holdase function that is mechanistically distinct from its NEF activity.

@article{doi101002pro70575,
    author = "Kidd, Justin M and Sun, Cancan and Garay, Alissa and Keplinger, Mitchell and Richter, Colin and May, Aaron E and Liu, Qinglian",
    title = "ATP modulates holdase activity of fungal and human 110-kilodalton heat shock proteins to promote protein folding.",
    year = "2026",
    journal = "Protein science: a publication of the Protein Society",
    abstract = {Heat shock proteins of the 70-kDa family (Hsp70s) are highly abundant and conserved molecular chaperones that help preserve proteostasis primarily by facilitating proper protein folding. Heat shock protein of the 110-kDa family (Hsp110s), a specialized branch of the Hsp70/Hsp110 superfamily, function both as nucleotide exchange factor (NEF) cochaperones for Hsp70s and as independent "holdase" chaperones that stabilize non-native polypeptides to prevent aggregation and facilitate downstream refolding by Hsp70s. While Hsp110 NEF activity is well characterized, the consequences of adenosine 5'-triphosphate (ATP) binding for Hsp110 holdase behavior have remained largely unexplored. Although holdase activity is generally considered nucleotide-independent, reports of ATP-dependent effects have raised questions about the underlying mechanism. Here, we examined the biochemical properties of Multicopy Suppressor of ira1 3 (Msi3), the sole Hsp110 in Candida albicans, to dissect the role of ATP in holdase function. We first identified an inhibitory effect of elevated Mg2+ concentrations on Msi3 holdase activity. This inhibitory effect is counteracted by the intrinsically disordered C-terminal segment, revealing a distinct stabilization role for this region, previously of unknown function. In addition, ATP alleviates inhibition by elevated Mg2+, providing an explanation for an apparent ATP-dependence observed previously. Interestingly, although dispensable for aggregation suppression, ATP modulates Msi3 holdase activity for refolding competence by broadening the concentration range over which it remains productive. Increasing Msi3 concentration improved overall downstream refolding recovery but slowed refolding kinetics, and ATP alleviated this kinetic constraint. Analyses of Hsp105, the major human Hsp110, suggest that these biochemical properties are largely conserved. Together, these findings suggest that ATP modulates Hsp110 holdase activity by tuning the balance between substrate sequestration and engagement dynamics, revealing an ATP-dependent regulatory dimension of Hsp110 holdase function that is mechanistically distinct from its NEF activity.},
    url = "https://pubmed.ncbi.nlm.nih.gov/42043290/",
    doi = "10.1002/pro.70575",
    pmid = "42043290"
}

Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core-shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled ~25 nm biomimetic polydopamine (PDA) coating. Triggered by elevated tumoral ATP levels, CZP undergoes coordination-induced disassembly and promotes oxidative stress amplification. Specifically, the PDA shell acts as a superoxide dismutase (SOD) mimetic to continuously supply H2O2, fueling Cu2+-mediated Fenton-like reactions to unleash highly toxic hydroxyl radicals (•OH) while aggressively depleting the intracellular glutathione (GSH) pool. This irreversible oxidative damage, coupled with Zn2+-induced mitochondrial dysfunction, triggers profound mitochondrial DNA (mtDNA) leakage. Crucially, this cytosolic DNA robustly activates the cGAS-STING signaling axis, driving a massive surge in immunogenic cell death (ICD) and significantly promoting dendritic cell (DC) maturation. Furthermore, CZP markedly inhibited primary tumor growth in vivo and showed protection in a tumor re-challenge model, accompanied by enhanced dendritic cell maturation. These findings support the potential of this ATP-responsive bimetallic nanoplatform to promote antitumor immune activation.

@article{doi103390jfb17040199,
    author = "Li, You and Zhang, Wenxin and Xu, Zitao and Ma, Shixin and Xiong, Yufei and Yu, Li and Gao, Huiling and Shu, Yang and Fei, Teng",
    title = "ATP-Responsive Bimetallic Metal-Organic Frameworks Amplify Oxidative Stress in the Tumor Microenvironment for Synergistic Chemo-Immunotherapy.",
    year = "2026",
    journal = "Journal of functional biomaterials",
    abstract = "Metal ion-based chemo-immunotherapy is often limited by rigid intracellular metal homeostasis, insufficient reactive oxygen species (ROS) accumulation, and an immunosuppressive tumor microenvironment (TME). To overcome these limitations, we engineered an ATP-responsive, core-shell bimetallic nanoreactor (Cu/ZIF@PDA, termed CZP) featuring a precisely controlled \textasciitilde 25 nm biomimetic polydopamine (PDA) coating. Triggered by elevated tumoral ATP levels, CZP undergoes coordination-induced disassembly and promotes oxidative stress amplification. Specifically, the PDA shell acts as a superoxide dismutase (SOD) mimetic to continuously supply H2O2, fueling Cu2+-mediated Fenton-like reactions to unleash highly toxic hydroxyl radicals (•OH) while aggressively depleting the intracellular glutathione (GSH) pool. This irreversible oxidative damage, coupled with Zn2+-induced mitochondrial dysfunction, triggers profound mitochondrial DNA (mtDNA) leakage. Crucially, this cytosolic DNA robustly activates the cGAS-STING signaling axis, driving a massive surge in immunogenic cell death (ICD) and significantly promoting dendritic cell (DC) maturation. Furthermore, CZP markedly inhibited primary tumor growth in vivo and showed protection in a tumor re-challenge model, accompanied by enhanced dendritic cell maturation. These findings support the potential of this ATP-responsive bimetallic nanoplatform to promote antitumor immune activation.",
    url = "https://pubmed.ncbi.nlm.nih.gov/42042305/",
    doi = "10.3390/jfb17040199",
    pmid = "42042305"
}