Extendable stapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde.

ABSTRACT: Peptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and bro

SUBMITTER: Li B 

PROVIDER: S-EPMC8760283 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature