Site‐ and Stereoselective Glycomodification of Biomolecules through Carbohydrate‐Promoted Pictet–Spengler Reaction

• DOI: 10.1002/anie.202401394
• Publication Date: 2024-02-24T05:29:35Z
• Authors: Bo Liu; Xiangman Zou; Yue Zhang; Yang Yang; Hao Xu; Feng Tang; Huixin Yu; Fei Xia; Zhi Liu; Jianwei Zhao; Wei Shi; Wei Huang
• Keywords: Glycobiology; Glycoconjugate; Biomolecule

Abstract Carbohydrates play pivotal roles in an array of essential biological processes and are consequently involved many diseases. To meet the needs glycobiology research, chemical enzymatic non‐enzymatic methods have been developed to generate glycoconjugates with well‐defined structures. Herein, harnessing unique properties C6‐oxidized glycans, we report a straightforward robust strategy for site‐ stereoselective glycomodification biomolecules N‐terminal tryptophan residues by carbohydrate‐promoted Pictet–Spengler reaction, which is not adapted typical aldehyde substrates under biocompatible conditions. This method reliably delivers highly homogeneous stable linkages thus has great potential functional modulation peptides proteins research. Moreover, this reaction can be performed at glycosites glycopeptides, glycoproteins living‐cell surfaces site‐specific manner. Control experiments indicated that protected α‐O atom donors free N−H bond tryptamine motif crucial reaction. Mechanistic investigations demonstrated exhibited first‐order dependence on both glycan, deprotonation/rearomatization pentahydro‐β‐carbolinium ion intermediate might rate‐determining step.