Sequence Diversification by Divergent C-Terminal Elongation of Peptides

J Org Chem. 2018 Feb 16;83(4):1797-1803. doi: 10.1021/acs.joc.7b02655. Epub 2018 Jan 25.

Abstract

Sequence diversification at the C terminus is traditionally limited by significant epimerization of the C-terminal residue during its activation toward nucleophilic attack, thus mandating repetition of the peptide synthesis for each targeted variation. Here, we accomplish divergent C-terminal elongation of a single peptide substrate with concomitant resin cleavage via displacement of an N-acyl urea moiety. Sterically hindered amino acids such as Ile and Pro are well-tolerated in this approach, which proceeds reasonable conversion and no detectable epimerization of the starting peptide's C-terminal amino acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / chemistry*
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Resins, Synthetic / chemistry
  • Urea / chemistry

Substances

  • Amino Acids
  • Peptides
  • Resins, Synthetic
  • Urea