Selective Native N_(in)-H Bond Activation in Peptides with Metallaphotocatalysis.

ABSTRACT: The development of chemical methods enabling site-selective incorporation of noncanonical amino acids into peptide backbones with precise functional tailoring remains a critical challenge. Particularly compelling is the use of underexplored endogenous amino acid hotspots, such as the N _(in) of tryptophan, as versatile anchors for diversification. Herein, we report a chemoselective N(sp²)-H bond activation strategy targeting native tryptophan residues within peptide frameworks, exemplified by GLP-1 (7-37), using nickel metallaphotocatalysis under postsynthetic solid-phase conditions. This selective N _(in)-arylation reaction proceeds efficiently within 3 h of light irradiation in highly functionalized heterogeneous environments, employing minima

SUBMITTER: Delgado JAC 

PROVIDER: S-EPMC12042047 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature