Highly efficient synthesis of sialylglycopeptides overcoming unexpected aspartimide formation during activation of Fmoc-Asn(undecadisialyloligosaccharide)-OH |
| |
Authors: | Naoki Yamamoto Tohru Sakakibara Yasuhiro Kajihara |
| |
Institution: | a Graduate School of Integrated Science, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan b Department of Cell Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, CNV-6, La Jolla, CA 92037, USA |
| |
Abstract: | Oligosaccharyl Fmoc-asparagine in which amide nitrogen of the asparagine side chain attached to the anomeric position at the reducing end, is a versatile building block and has been used for various glycopeptide synthesis using Fmoc solid-phase peptide synthesis (SPPS). We found unexpected aspartimide formation between amide nitrogen at the reducing end and α-carboxyl acid of oligosaccharyl Fmoc-asparagine during activation of α-carboxyl acid and this side reaction resulted in low coupling yields of oligosaccharyl Fmoc-asparagine with peptide-resin. This aspartimide formed efficiently using conventional coupling reagents such as PyBOP and HATU, but DEPBT afforded little of the aspartimide derivative. Activation condition using DEPBT (3.0 equiv) and DIPEA (2.0 equiv) afforded excellent yield (97%) in coupling reaction between Fmoc-Asn(CHO)-OH and peptide-resin. Based on these results, we performed a synthesis of a sialylglycopeptide, HIV-gp120 (54-63) VVLLVN(CHO)VTENF, in high yield. |
| |
Keywords: | Solid-phase glycopeptide synthesis Sialylglycopeptide Aspartimide formation |
本文献已被 ScienceDirect 等数据库收录! |
|