Late-Stage Tryptophan Modification of Native Peptides through Photochemical Indole-to-Quinazoline Editing

Site-specific late-stage modification of native peptides is an appealing strategy for generating analogues of bioactive peptides in effort- and cost-effective manner. The concept of skeletal editing emerging recently is attractive for developing new generation of late-stage peptide modification methods. In this work, we developed a facile tryptophan-specific late-stage peptide modification based on photocatalytic indole-to-quinazoline editing. The method showed broad scope on both linear and cyclic peptide substrates and was applied to the modification of commercially available peptide drugs. A mechanism based on singlet oxygen oxidation of tryptophan and interruption of oxidative indole cleavage by ammonia addition was proposed.