Peptide synthesis

@book{crossref1972macromolecules,
    title = "Macromolecules and Behavior",
    year = "1972",
    url = "https://doi.org/10.1007/978-1-4684-6042-1",
    doi = "10.1007/978-1-4684-6042-1"
}

@article{bondareff1975macromolecules,
    author = "Bondareff, William",
    title = "Macromolecules and behavior",
    year = "1975",
    journal = "Electroencephalography and Clinical Neurophysiology",
    url = "https://doi.org/10.1016/0013-4694(75)90239-4",
    doi = "10.1016/0013-4694(75)90239-4",
    number = "2",
    pages = "223",
    volume = "38"
}

@article{fox1980the,
    author = "Fox, Sidney W.",
    title = "The origins of behavior in macromolecules and protocells",
    year = "1980",
    journal = "Comparative Biochemistry and Physiology Part B: Comparative Biochemistry",
    url = "https://doi.org/10.1016/0305-0491(80)90330-2",
    doi = "10.1016/0305-0491(80)90330-2",
    number = "3",
    pages = "423-436",
    volume = "67"
}

@misc{fox1980the1,
    author = "Fox, S. W",
    title = "The origins of behavior in macromolecules and protocells",
    year = "1980",
    howpublished = "Comparative Biochemistry and Physiology, v. 67B, p. 423-436",
    note = "talkorigins\_source = {true}; raw\_reference = {Fox, S. W., 1980, The origins of behavior in macromolecules and protocells: Comparative Biochemistry and Physiology, v. 67B, p. 423-436.}"
}

@book{crossref1982behavior,
    title = "Behavior of Macromolecules",
    year = "1982",
    booktitle = "Advances in Polymer Science",
    url = "https://doi.org/10.1007/bfb0023982",
    doi = "10.1007/bfb0023982"
}

@incollection{dunn1982macromolecules,
    author = "Dunn, Adrian J.",
    title = "MACROMOLECULES AND BEHAVIOR",
    year = "1982",
    booktitle = "Molecular Approaches to Neurobiology",
    url = "https://doi.org/10.1016/b978-0-12-137020-6.50017-1",
    doi = "10.1016/b978-0-12-137020-6.50017-1",
    pages = "317-340"
}

@article{fox1984selfsequencing,
    author = "Fox, Sidney W.",
    title = "Self-sequencing of amino acids and origins of polyfunctional protocells",
    year = "1984",
    journal = "Origins of Life",
    url = "https://doi.org/10.1007/bf00933695",
    doi = "10.1007/bf00933695",
    number = "1-4",
    pages = "485-488",
    volume = "14"
}

The materials properties of mica have surprising similarities to those of living systems. The mica hypothesis is that life could have originated between mica sheets, which provide stable compartments, mechanical energy for bond formation, and the isolation needed for Darwinian evolution. Mechanical energy is produced by the movement of mica sheets, in response to forces such as ocean currents or temperature changes. The energy of a carbon-carbon bond at room temperature is comparable to a mechanical force of 6 nanoNewtons (nN) moving a distance of 100 picometers. Mica's movements may have facilitated mechanochemistry, resulting in the synthesis of prebiotic organic molecules. Furthermore, mica's movements may have facilitated the earliest cell divisions, at a later stage of life's origins. Mica's movements, pressing on lipid vesicles containing proto-cellular macromolecules, might have facilitated the blebbing off of ‘daughter’ protocells. This blebbing-off process has been observed recently in wall-less L-form bacteria and is proposed to be a remnant of the earliest cell divisions (Leaver, et al. Nature 457, 849 (2009).

@article{doi101557proc1185ii0315,
    author = "Hansma, H.",
    title = "Could Life Originate between Mica Sheets?: Mechanochemical Biomolecular Synthesis and the Origins of Life",
    year = "2009",
    journal = "MRS Proceedings",
    abstract = "The materials properties of mica have surprising similarities to those of living systems. The mica hypothesis is that life could have originated between mica sheets, which provide stable compartments, mechanical energy for bond formation, and the isolation needed for Darwinian evolution. Mechanical energy is produced by the movement of mica sheets, in response to forces such as ocean currents or temperature changes. The energy of a carbon-carbon bond at room temperature is comparable to a mechanical force of 6 nanoNewtons (nN) moving a distance of 100 picometers. Mica's movements may have facilitated mechanochemistry, resulting in the synthesis of prebiotic organic molecules. Furthermore, mica's movements may have facilitated the earliest cell divisions, at a later stage of life's origins. Mica's movements, pressing on lipid vesicles containing proto-cellular macromolecules, might have facilitated the blebbing off of ‘daughter’ protocells. This blebbing-off process has been observed recently in wall-less L-form bacteria and is proposed to be a remnant of the earliest cell divisions (Leaver, et al. Nature 457, 849 (2009).",
    url = "https://www.semanticscholar.org/paper/edbcfe286db909f395c8ee9c0968ffc9ae8ec76e",
    doi = "10.1557/PROC-1185-II03-15",
    is_oa = "true",
    semanticscholar_citation_count = "5",
    semanticscholar_id = "edbcfe286db909f395c8ee9c0968ffc9ae8ec76e",
    volume = "1185"
}

@article{gleiser2009toward,
    author = "Gleiser, Marcelo and Walker, Sara Imari",
    title = "Toward Homochiral Protocells in Noncatalytic Peptide Systems",
    year = "2009",
    journal = "Origins of Life and Evolution of Biospheres",
    url = "https://doi.org/10.1007/s11084-009-9166-5",
    doi = "10.1007/s11084-009-9166-5",
    number = "5",
    pages = "479-493",
    volume = "39"
}

@article{doi101021ol301723e,
    author = "Zhang, Yalong and Muthana, Saddam M and Barchi, J. and Gildersleeve, J.",
    title = "Divergent behavior of glycosylated threonine and serine derivatives in solid phase peptide synthesis.",
    year = "2012",
    journal = "Organic letters",
    url = "https://europepmc.org/articles/pmc3417326?pdf=render",
    doi = "10.1021/ol301723e",
    is_oa = "true",
    number = "15",
    pages = "3958-3961",
    semanticscholar_citation_count = "17",
    semanticscholar_id = "6a91f832a00d617293248517839452ddecc2d583",
    volume = "14"
}

@article{doi101021bm500436p,
    author = "Pechar, M. and Pola, R. and Laga, R. and Braunova, A. and Filippov, S. and Bogomolova, A. and Bednárová, L. and Vaněk, O. and Ulbrich, K.",
    title = "Coiled coil peptides and polymer-peptide conjugates: synthesis, self-assembly, characterization and potential in drug delivery systems.",
    year = "2014",
    journal = "Biomacromolecules",
    url = "https://www.semanticscholar.org/paper/c6b76e2c8818aa3ae67bde1efc51398db6039b7a",
    doi = "10.1021/bm500436p",
    is_oa = "true",
    number = "7",
    pages = "2590-2599",
    semanticscholar_citation_count = "34",
    semanticscholar_id = "c6b76e2c8818aa3ae67bde1efc51398db6039b7a",
    volume = "15"
}

@article{doi101016jbpj201611048,
    author = "Chilkoti, A.",
    title = "Phase Behavior and Self-Assembly of a New Family of Stimulus Responsive Peptide Polymers",
    year = "2017",
    journal = "Biophysical Journal",
    url = "http://www.cell.com/article/S0006349516310785/pdf",
    doi = "10.1016/J.BPJ.2016.11.048",
    is_oa = "true",
    number = "3",
    pages = "5a",
    semanticscholar_id = "d007489db2794aa6c1c787f19001160bfe1c5b8b",
    volume = "112"
}

Abstract How and where did life on Earth originate? To date, various environments have been proposed as plausible sites for the origin of life. However, discussions have focused on a limited stage of chemical evolution, or emergence of a specific chemical function of proto-biological systems. It remains unclear what geochemical situations could drive all the stages of chemical evolution, ranging from condensation of simple inorganic compounds to the emergence of self-sustaining systems that were evolvable into modern biological ones. In this review, we summarize reported experimental and theoretical findings for prebiotic chemistry relevant to this topic, including availability of biologically essential elements (N and P) on the Hadean Earth, abiotic synthesis of life's building blocks (amino acids, peptides, ribose, nucleobases, fatty acids, nucleotides, and oligonucleotides), their polymerizations to bio-macromolecules (peptides and oligonucleotides), and emergence of biological functions of replication and compartmentalization. It is indicated from the overviews that completion of the chemical evolution requires at least eight reaction conditions of (1) reductive gas phase, (2) alkaline pH, (3) freezing temperature, (4) fresh water, (5) dry/dry-wet cycle, (6) coupling with high energy reactions, (7) heating-cooling cycle in water, and (8) extraterrestrial input of life's building blocks and reactive nutrients. The necessity of these mutually exclusive conditions clearly indicates that life's origin did not occur at a single setting; rather, it required highly diverse and dynamic environments that were connected with each other to allow intra-transportation of reaction products and reactants through fluid circulation. Future experimental research that mimics the conditions of the proposed model are expected to provide further constraints on the processes and mechanisms for the origin of life.

@article{doi101016jgsf201707007,
    author = "Kitadai, N. and Maruyama, S.",
    title = "Origins of building blocks of life: A review",
    year = "2017",
    journal = "Geoscience Frontiers",
    abstract = "Abstract How and where did life on Earth originate? To date, various environments have been proposed as plausible sites for the origin of life. However, discussions have focused on a limited stage of chemical evolution, or emergence of a specific chemical function of proto-biological systems. It remains unclear what geochemical situations could drive all the stages of chemical evolution, ranging from condensation of simple inorganic compounds to the emergence of self-sustaining systems that were evolvable into modern biological ones. In this review, we summarize reported experimental and theoretical findings for prebiotic chemistry relevant to this topic, including availability of biologically essential elements (N and P) on the Hadean Earth, abiotic synthesis of life's building blocks (amino acids, peptides, ribose, nucleobases, fatty acids, nucleotides, and oligonucleotides), their polymerizations to bio-macromolecules (peptides and oligonucleotides), and emergence of biological functions of replication and compartmentalization. It is indicated from the overviews that completion of the chemical evolution requires at least eight reaction conditions of (1) reductive gas phase, (2) alkaline pH, (3) freezing temperature, (4) fresh water, (5) dry/dry-wet cycle, (6) coupling with high energy reactions, (7) heating-cooling cycle in water, and (8) extraterrestrial input of life's building blocks and reactive nutrients. The necessity of these mutually exclusive conditions clearly indicates that life's origin did not occur at a single setting; rather, it required highly diverse and dynamic environments that were connected with each other to allow intra-transportation of reaction products and reactants through fluid circulation. Future experimental research that mimics the conditions of the proposed model are expected to provide further constraints on the processes and mechanisms for the origin of life.",
    url = "https://doi.org/10.1016/j.gsf.2017.07.007",
    doi = "10.1016/J.GSF.2017.07.007",
    is_oa = "true",
    number = "4",
    pages = "1117-1153",
    semanticscholar_citation_count = "349",
    semanticscholar_id = "b0926c65e24d5418043226bdf1055eaf2178a79e",
    volume = "9"
}

@article{doi101016jijbiomac201701001,
    author = "Shouji, Takuya and Yamamoto, Kazuya and Kadokawa, J.",
    title = "Chemoenzyamtic synthesis and self-assembling gelation behavior of amylose-grafted poly(γ-glutamic acid).",
    year = "2017",
    journal = "International journal of biological macromolecules",
    url = "https://www.semanticscholar.org/paper/cf168effbc0e27ac8afc780c4f8cf6d2d3c4195e",
    doi = "10.1016/j.ijbiomac.2017.01.001",
    is_oa = "true",
    pages = "99-105",
    semanticscholar_citation_count = "14",
    semanticscholar_id = "cf168effbc0e27ac8afc780c4f8cf6d2d3c4195e",
    volume = "97"
}

This tutorial review describes molecular design principles for peptides and peptide derivatives undergoing phase separation and highlights the potential of the resulting coacervate protocells.

@article{abbas2021peptidebased,
    author = "Abbas, Manzar and Lipiński, Wojciech P. and Wang, Jiahua and Spruijt, Evan",
    title = "Peptide-based coacervates as biomimetic protocells",
    year = "2021",
    journal = "Chemical Society Reviews",
    abstract = "This tutorial review describes molecular design principles for peptides and peptide derivatives undergoing phase separation and highlights the potential of the resulting coacervate protocells.",
    url = "https://doi.org/10.1039/d0cs00307g",
    doi = "10.1039/d0cs00307g",
    number = "6",
    pages = "3690-3705",
    volume = "50"
}

The origin of the genetic code is an abiding mystery in biology. Hints of a 'code within the codons' suggest biophysical interactions, but these patterns have resisted interpretation. Here, we present a new framework, grounded in the autotrophic growth of protocells from CO2 and H2. Recent work suggests that the universal core of metabolism recapitulates a thermodynamically favoured protometabolism right up to nucleotide synthesis. Considering the genetic code in relation to an extended protometabolism allows us to predict most codon assignments. We show that the first letter of the codon corresponds to the distance from CO2 fixation, with amino acids encoded by the purines (G followed by A) being closest to CO2 fixation. These associations suggest a purine-rich early metabolism with a restricted pool of amino acids. The second position of the anticodon corresponds to the hydrophobicity of the amino acid encoded. We combine multiple measures of hydrophobicity to show that this correlation holds strongly for early amino acids but is weaker for later species. Finally, we demonstrate that redundancy at the third position is not randomly distributed around the code: non-redundant amino acids can be assigned based on size, specifically length. We attribute this to additional stereochemical interactions at the anticodon. These rules imply an iterative expansion of the genetic code over time with codon assignments depending on both distance from CO2 and biophysical interactions between nucleotide sequences and amino acids. In this way the earliest RNA polymers could produce non-random peptide sequences with selectable functions in autotrophic protocells.

@article{doi101016jbbabio2022148597,
    author = "Harrison, S. and Palmeira, Raquel Nunes and Halpern, Aaron and Lane, N.",
    title = "A biophysical basis for the emergence of the genetic code in protocells.",
    year = "2022",
    journal = "Biochimica et biophysica acta. Bioenergetics",
    abstract = "The origin of the genetic code is an abiding mystery in biology. Hints of a 'code within the codons' suggest biophysical interactions, but these patterns have resisted interpretation. Here, we present a new framework, grounded in the autotrophic growth of protocells from CO2 and H2. Recent work suggests that the universal core of metabolism recapitulates a thermodynamically favoured protometabolism right up to nucleotide synthesis. Considering the genetic code in relation to an extended protometabolism allows us to predict most codon assignments. We show that the first letter of the codon corresponds to the distance from CO2 fixation, with amino acids encoded by the purines (G followed by A) being closest to CO2 fixation. These associations suggest a purine-rich early metabolism with a restricted pool of amino acids. The second position of the anticodon corresponds to the hydrophobicity of the amino acid encoded. We combine multiple measures of hydrophobicity to show that this correlation holds strongly for early amino acids but is weaker for later species. Finally, we demonstrate that redundancy at the third position is not randomly distributed around the code: non-redundant amino acids can be assigned based on size, specifically length. We attribute this to additional stereochemical interactions at the anticodon. These rules imply an iterative expansion of the genetic code over time with codon assignments depending on both distance from CO2 and biophysical interactions between nucleotide sequences and amino acids. In this way the earliest RNA polymers could produce non-random peptide sequences with selectable functions in autotrophic protocells.",
    url = "https://doi.org/10.1016/j.bbabio.2022.148597",
    doi = "10.1016/j.bbabio.2022.148597",
    is_oa = "true",
    number = "8",
    pages = "148597",
    semanticscholar_citation_count = "23",
    semanticscholar_id = "b1aedb16674cef21033ef71aa63c71450c627085",
    volume = "1863"
}

Condensed coacervate phases are now understood to be important features of modern cell biology, as well as valuable protocellular models in origin of life studies and synthetic biology. In each of these fields, the development of model systems with varied and tuneable material properties is of great importance for replicating properties of life. Here, we develop a ligase ribozyme system capable of concatenating short RNA fragments into extremely long chains. Our results show that formation of coacervate microdroplets with the ligase ribozyme and poly(L-lysine) enhances ribozyme rate and yield, which in turn increases the length of the anionic polymer component of the system and imparts specific physical properties to the droplets. Droplets containing active ribozyme sequences resist growth, do not wet or spread on unpassivated surfaces, and exhibit reduced transfer of RNA between droplets when compared to controls containing inactive sequences. These altered behaviours, which stem from RNA sequence and catalytic activity, constitute a specific phenotype and potential fitness advantage, opening the door to selection and evolution experiments based on a genotype – phenotype linkage.

@misc{vay2022ribozymephenotype,
    author = "Vay, Kristian Le and Salibi, Elia and Ghosh, Basusree and Dora Tang, T-Y and Mutschler, Hannes",
    title = "Ribozyme-phenotype coupling in peptide-based coacervate protocells",
    year = "2022",
    abstract = "Condensed coacervate phases are now understood to be important features of modern cell biology, as well as valuable protocellular models in origin of life studies and synthetic biology. In each of these fields, the development of model systems with varied and tuneable material properties is of great importance for replicating properties of life. Here, we develop a ligase ribozyme system capable of concatenating short RNA fragments into extremely long chains. Our results show that formation of coacervate microdroplets with the ligase ribozyme and poly(L-lysine) enhances ribozyme rate and yield, which in turn increases the length of the anionic polymer component of the system and imparts specific physical properties to the droplets. Droplets containing active ribozyme sequences resist growth, do not wet or spread on unpassivated surfaces, and exhibit reduced transfer of RNA between droplets when compared to controls containing inactive sequences. These altered behaviours, which stem from RNA sequence and catalytic activity, constitute a specific phenotype and potential fitness advantage, opening the door to selection and evolution experiments based on a genotype – phenotype linkage.",
    url = "https://doi.org/10.1101/2022.10.25.513667",
    doi = "10.1101/2022.10.25.513667"
}

@article{zhuravskaya2022synthesis,
    author = "Zhuravskaya, O. N. and Dommes, O. A. and Okatova, O. V. and Panarin, E. F. and Pavlov, G. M.",
    title = "Synthesis and Hydrodynamic Behavior of Poly(methacryloylamino galactose) Macromolecules",
    year = "2022",
    journal = "Doklady Physical Chemistry",
    url = "https://doi.org/10.1134/s0012501622030022",
    doi = "10.1134/s0012501622030022",
    number = "1",
    pages = "35-38",
    volume = "503"
}

Membraneless compartments formed through liquid-liquid phase separation (LLPS) of intrinsically disordered proteins are essential for cellular organization and regulation. Similarly, short peptide-based coacervates assembled via LLPS may have served as primitive compartments during early biochemical evolution. However, the molecular grammar that governs the phase behavior of short peptides remains elusive. Here, we present a library of short cysteine-terminated peptides that act as "sticker" units to systematically investigate the phase separation behavior of their oxidized dimeric forms. Our findings reveal that LLPS in these simple peptide systems is primarily determined by the apparent ratio of arginine to aromatic residues (Rarg/aro) and by the specific identity of the aromatic residue (Phe, Tyr, Trp). The measured saturation concentrations (Csat) exhibit a linear correlation with the hydrophobicity of the aromatic residues, indicating that increased hydrophobicity enhances the driving force for phase separation. To demonstrate their functional versatility and relevance as protocell models, we incorporated an enzyme-inspired catalytic triad (Ser-His-Asp, SHD) into the peptide sequences, thereby imparting catalytic activity to the coacervates. Moreover, redox-active disulfide spacers enabled reversible condensation and dissolution in response to glutathione, facilitating intracellular delivery and glutathione-triggered release of cargos such as mRNA. Together, these findings establish a minimal yet predictive framework for the design of peptide-based coacervates and highlight their potential in intracellular delivery, mRNA vaccines, and studies on the chemical origins of life.

@article{doi101016jjcis2025139604,
    author = "Wang, Jiahua and Abbas, Manzar and Qiu, Yuening and Zhao, Yao and Wang, Junyou and Li, Yuehua",
    title = "Sequence-encoded phase behavior and functionality of short peptide coacervates.",
    year = "2025",
    journal = "Journal of colloid and interface science",
    abstract = {Membraneless compartments formed through liquid-liquid phase separation (LLPS) of intrinsically disordered proteins are essential for cellular organization and regulation. Similarly, short peptide-based coacervates assembled via LLPS may have served as primitive compartments during early biochemical evolution. However, the molecular grammar that governs the phase behavior of short peptides remains elusive. Here, we present a library of short cysteine-terminated peptides that act as "sticker" units to systematically investigate the phase separation behavior of their oxidized dimeric forms. Our findings reveal that LLPS in these simple peptide systems is primarily determined by the apparent ratio of arginine to aromatic residues (Rarg/aro) and by the specific identity of the aromatic residue (Phe, Tyr, Trp). The measured saturation concentrations (Csat) exhibit a linear correlation with the hydrophobicity of the aromatic residues, indicating that increased hydrophobicity enhances the driving force for phase separation. To demonstrate their functional versatility and relevance as protocell models, we incorporated an enzyme-inspired catalytic triad (Ser-His-Asp, SHD) into the peptide sequences, thereby imparting catalytic activity to the coacervates. Moreover, redox-active disulfide spacers enabled reversible condensation and dissolution in response to glutathione, facilitating intracellular delivery and glutathione-triggered release of cargos such as mRNA. Together, these findings establish a minimal yet predictive framework for the design of peptide-based coacervates and highlight their potential in intracellular delivery, mRNA vaccines, and studies on the chemical origins of life.},
    url = "https://www.semanticscholar.org/paper/a1724ff70fe9b1052276f3add7d5f2fd750bf13c",
    doi = "10.1016/j.jcis.2025.139604",
    is_oa = "true",
    pages = "139604",
    semanticscholar_citation_count = "3",
    semanticscholar_id = "a1724ff70fe9b1052276f3add7d5f2fd750bf13c",
    volume = "706"
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The original conditions from which primitive life emerged on the early Earth were likely to be dilute mixtures of organic compounds in aqueous solutions. A significant challenge for origins of life research is to discover the reactions that allowed such mixtures to become increasingly complex with products such as polymers that had structural and functional properties related to biology. The chances are low that potential reactants could find one another in dilute solutions composed of thousands of different molecular species. To improve the probability of such encounters, we have investigated a novel condition that both concentrates and organizes potential reactants and encapsulates polymeric products to form protocells. The condition involves a source of freshwater that falls as rainfall precipitation on land masses such as volcanic islands. The water dissolves exogenously and endogenously available organic compounds and feeds into hydrothermal fields where the solutions undergo cycles of evaporation and rehydration, a process easily observed today. Most researchers would agree that monomers such as amino acids and nucleotides would be present in the mixture, but less attention has been paid to the self-assembly of amphiphilic compounds that are also essential components of widely studied protocells. Here, we hypothesize how a closely related medium--multilamellar lipid-polymer (LP) matrices exposed to wet-dry cycles--can act as a progenitor and drive three essential processes: concentration of monomers, polymerization by synthesis of ester and peptide bonds, and promotion of interactions between peptides and nucleotide oligomers. We propose that such matrices represent "combinatorial engines" that can generate otherwise improbable functional complexes. After characterizing the sources of organics, the geochemical settings, and energetic environments in which such an LP progenitor can assemble, we present a conceptual model system that informs both chemical and computational experimental approaches to test this hypothesis.

@article{doi10117715311074261428661,
    author = "Damer, B. and Deamer, David",
    title = "A Multilamellar Lipid-Polymer Progenitor Can Promote the Assembly of Improbable Functional Polymer Complexes at Life's Origins.",
    year = "2026",
    journal = "Astrobiology",
    abstract = {The original conditions from which primitive life emerged on the early Earth were likely to be dilute mixtures of organic compounds in aqueous solutions. A significant challenge for origins of life research is to discover the reactions that allowed such mixtures to become increasingly complex with products such as polymers that had structural and functional properties related to biology. The chances are low that potential reactants could find one another in dilute solutions composed of thousands of different molecular species. To improve the probability of such encounters, we have investigated a novel condition that both concentrates and organizes potential reactants and encapsulates polymeric products to form protocells. The condition involves a source of freshwater that falls as rainfall precipitation on land masses such as volcanic islands. The water dissolves exogenously and endogenously available organic compounds and feeds into hydrothermal fields where the solutions undergo cycles of evaporation and rehydration, a process easily observed today. Most researchers would agree that monomers such as amino acids and nucleotides would be present in the mixture, but less attention has been paid to the self-assembly of amphiphilic compounds that are also essential components of widely studied protocells. Here, we hypothesize how a closely related medium--multilamellar lipid-polymer (LP) matrices exposed to wet-dry cycles--can act as a progenitor and drive three essential processes: concentration of monomers, polymerization by synthesis of ester and peptide bonds, and promotion of interactions between peptides and nucleotide oligomers. We propose that such matrices represent "combinatorial engines" that can generate otherwise improbable functional complexes. After characterizing the sources of organics, the geochemical settings, and energetic environments in which such an LP progenitor can assemble, we present a conceptual model system that informs both chemical and computational experimental approaches to test this hypothesis.},
    url = "https://www.semanticscholar.org/paper/dabf98ba97209ef0aa5dcccbb7b6ad218f837f04",
    doi = "10.1177/15311074261428661",
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