Tunable Electrochemical Peptide Modifications: Unlocking New Levels of Orthogonality for Side-Chain Functionalization.

ABSTRACT: Electrochemical transformations provide enticing opportunities for programmable, residue-specific peptide modifications. Herein, we harness the potential of amidic side-chains as underutilized handles for late-stage modification through the development of an electroauxiliary-assisted oxidation of glutamine residues within unprotected peptides. Glutamine building blocks bearing electroactive side-chain N,S-acetals are incorporated into peptides using standard Fmoc-SPPS. Anodic oxidation of the electroauxiliary in the presence of diverse alcohol nucleophiles enables the installation of high-value N,O-acetal functionalities. Proof-of-principle for an electrochemical peptide stapling protocol, as well as the functionalization of dynorphin B, an endogenous opioid peptide, demonstrates the appli

SUBMITTER: Karipal Padinjare Veedu D 

PROVIDER: S-EPMC10107541 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature