Selective peptide bond formation via side chain reactivity and self-assembly of abiotic phosphates.

ABSTRACT: In the realm of biology, peptide bonds are formed via reactive phosphate-containing intermediates, facilitated by compartmentalized environments that ensure precise coupling and folding. Herein, we use aminoacyl phosphate esters, synthetic counterparts of biological aminoacyl adenylates, that drive selective peptide bond formation through side chain-controlled reactivity and self-assembly. This strategy results in the preferential incorporation of positively charged amino acids from mixtures containing natural and non-natural amino acids during the spontaneous formation of amide bonds in water. Conversely, aminoacyl phosphate esters that lack assembly and exhibit fast reactivity result in random peptide coupling. By introducing structural modifications to the phosphate esters (ethyl vs. ph

SUBMITTER: Sharma A 

PROVIDER: S-EPMC11790832 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature