Peptide Backbone Editing via Post-Translational O to C Acyl Shift.

ABSTRACT: Despite tremendous efforts to engineer translational machinery, replacing the encoded peptide backbone with new-to-nature structures remains a significant challenge. C, H, O, and N are the elements of life, yet ribosomes are capable of forming only C-N bonds as amides, C-O bonds as esters, and C-S bonds as thioesters. There is no current strategy to site-selectively form C-C bonds as ketones embedded in the backbones of ribosomal products. As an alternative to direct ribosomal C-C bond formation, here we report that peptides containing a dehydrolactic acid motif rapidly isomerize to generate backbone-embedded α,γ-diketoamides via a spontaneous formal O to C acyl shift rearrangement. The dehydrolactic acid motif can be introduced into peptides ribosomally or via solid-phase synthesis using

SUBMITTER: Schissel CK 

PROVIDER: S-EPMC11869294 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature