Ortho-Phthalaldehyde (OPA)-based chemoselective protein bioconjugation and peptide cyclization

Abstract

Ortho-Phthalaldehyde (OPA)-amine reaction and OPA-amine-thiol reaction have been developed to effectively modify native peptides and proteins under the physiological conditions. First, OPA and its derivatives can rapidly and smoothly react with primary amine moieties in peptides and proteins to achieve native protein biconjugations. Furthermore, OPA-alkyne bifunctional linkers can be used for proteome profiling. Second, OPA-amine-thiol three-component reaction has been developed for chemoselective peptide cyclization, directly on unprotected peptides in the aqueous buffer. Moreover, this OPA-guided cyclic peptide can be further modified with the N-maleimide moiety in one pot to introduce additional functionalities. The development of this OPA based chemoselective bioconjugation and peptide cyclization extends the toolbox for protein chemical modification and construction of cyclic peptides.