Work

Copper-Mediated Cross-Coupling Selective for Pyroglutamate Post-Translational Modifications

Year: 2024

Type: article

Abstract: Pyroglutamate is a cyclic N-terminal posttranslational modifica-tion that occurs in both proteins and peptide hormones. The prevalence and biological roles of pyroglutamate are little under-stood, in part due to limited tools to identify, quantify, and ma-nipulate its pyrrolidinone structure. Selective modification of pyroglutamate residues in complex polypeptides may provide unique tools to better understand its biological roles, and to al-low late-stage diversification of biologically active pyrogluta-mate-containing sequences. This work describes a copper-catalyzed N–H cross-coupling of unprotected peptides that is selective for N-terminal pyroglutamate residues. The reaction is operationally simple under mild conditions, and tolerates almost all canonical residues. Mechanistic studies point to a key role for a multidentate copper-binding mode of the extended polypeptide structure in delivering the observed reactivity. The reaction al-lows direct labeling and identification of a pyroglutamate hormone present in porcine intestinal extracts.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.4c10903

Authors: Yuxuan Ding, Yuecheng Jiang, Nicolas Lorenzo Serrat, Kangbao Zhong, Yu Lan, Zachary T. Ball

Institutions: Rice University, Henan Normal University, Zhengzhou University

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Welch Foundation, Division of Chemistry

Awards: G4108670466, G850697743