Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water.

ABSTRACT: The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pK_a primary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5-9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as β- and γ-pepti

SUBMITTER: Singh J 

PROVIDER: S-EPMC9204760 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature