The aspartimide problem in Fmoc-based SPPS. Part I

被引：95

作者：

Mergler, M ^{[1
]}

Dick, F ^{[1
]}

Sax, B ^{[1
]}

Weiler, P ^{[1
]}

Vorherr, T ^{[1
]}

机构：

[1] Bachem AG, CH-4416 Bubendorf, Switzerland

来源：

JOURNAL OF PEPTIDE SCIENCE | 2003年 / 9卷 / 01期

关键词：

aspartimide formation; Fmoc-solid phase peptide synthesis; Asp beta-carboxy protection; backbone protection; Asp-Gly motif; carboxy protection by orthoester formation;

D O I：

10.1002/psc.430

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A variety of Asp beta-carboxy protecting groups, Hmb backbone protection and a range of Fmoe cleavage protocols have been employed in syntheses of the model hexapeptide II-KDGYI-OH to investigate the aspartimide problem in more detail. The extent of formation of aspartimide and aspartimide-related by-products was determined by RP-HPLC. This study included three new Fmoc-Asp-OH derivatives: the beta-(4-pytidyl-diphenylmethyl) and beta-(9-phenyl-fluoren-9-yl) esters and also the orthoester Fmoc-beta-(4-methyl-2,6,7-trioxabicyclo[2.2.2]-oct-1-yl)-alanine. 3-Methylpent-3-yl protcction of the Asp side chain resulted in significant improvements with respect to aspartimide formation. Complete suppressionwas achieved using the combination OtBu side chain protection and limb backbone protection for the preceding Gly residue. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.

引用

页码：36 / 46

页数：11

共 12 条

[1] Stereoselective synthesis of threo and erythroβ-hydroxy and β-disubstituted-β-hydroxy α-amino acids [J].