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Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions.
Proc Natl Acad Sci U S A 2019; 116(33):16338-16346PN

Abstract

Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine-linked, analogous to today's proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein-RNA and protein-DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life.

Authors+Show Affiliations

National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332. NASA Center for the Origins of Life, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332. NASA Center for the Origins of Life, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332; lleman@scripps.edu loren.williams@chemistry.gatech.edu. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.National Science Foundation (NSF)-National Aeronautics and Space Administration (NASA) Center for Chemical Evolution, Atlanta, GA 30332; lleman@scripps.edu loren.williams@chemistry.gatech.edu. School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332. NASA Center for the Origins of Life, Georgia Institute of Technology, Atlanta, GA 30332.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31358633

Citation

Frenkel-Pinter, Moran, et al. "Selective Incorporation of Proteinaceous Over Nonproteinaceous Cationic Amino Acids in Model Prebiotic Oligomerization Reactions." Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 33, 2019, pp. 16338-16346.
Frenkel-Pinter M, Haynes JW, C M, et al. Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. Proc Natl Acad Sci USA. 2019;116(33):16338-16346.
Frenkel-Pinter, M., Haynes, J. W., C, M., Petrov, A. S., Burcar, B. T., Krishnamurthy, R., ... Williams, L. D. (2019). Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. Proceedings of the National Academy of Sciences of the United States of America, 116(33), pp. 16338-16346. doi:10.1073/pnas.1904849116.
Frenkel-Pinter M, et al. Selective Incorporation of Proteinaceous Over Nonproteinaceous Cationic Amino Acids in Model Prebiotic Oligomerization Reactions. Proc Natl Acad Sci USA. 2019 Aug 13;116(33):16338-16346. PubMed PMID: 31358633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. AU - Frenkel-Pinter,Moran, AU - Haynes,Jay W, AU - C,Martin, AU - Petrov,Anton S, AU - Burcar,Bradley T, AU - Krishnamurthy,Ramanarayanan, AU - Hud,Nicholas V, AU - Leman,Luke J, AU - Williams,Loren Dean, Y1 - 2019/07/29/ PY - 2019/7/31/pubmed PY - 2019/7/31/medline PY - 2019/7/31/entrez KW - chemical evolution KW - condensation dehydration KW - depsipeptides KW - peptide evolution KW - prebiotic chemistry SP - 16338 EP - 16346 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 116 IS - 33 N2 - Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine-linked, analogous to today's proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein-RNA and protein-DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/31358633/Selective_incorporation_of_proteinaceous_over_nonproteinaceous_cationic_amino_acids_in_model_prebiotic_oligomerization_reactions L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=31358633 DB - PRIME DP - Unbound Medicine ER -