3-thiopropionic acid as a highly versatile multidetachable thioester resin linker

被引:36
作者
Camarero, JA [1 ]
Adeva, A [1 ]
Muir, TW [1 ]
机构
[1] Rockefeller Univ, Lab Synthet Prot Chem, New York, NY 10021 USA
来源
LETTERS IN PEPTIDE SCIENCE | 2000年 / 7卷 / 01期
关键词
C-terminal modified peptides; hydrazides; hydroxamates; multidetachable resin; solid-phase peptide synthesis; thioester handle;
D O I
10.1007/BF02443557
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
This paper describes a practical new use of 3-mercaptopropionic acid as a highly versatile multidetachable linker for solid-phase synthesis. Our approach is based on the stability of the alkylthioester functionality to optimized Boc-SPPS protocols and HF treatment, as well as on the mild activation of the thioester functionality toward nucleophilic or reductive displacement. This allows several C-terminal modifications to be introduced into a synthetic molecule during the cleavage step. We have shown that unprotected peptides can be efficiently cleaved from a propyl thioester-polyethylene glycol-poly-(N,N-dimethylacrylamide) copolymer resin using a great variety of nucleophiles to give the corresponding C-terminally modified peptides (esters, thioesters, carboxylic acids, thioacids, amides, hydroxamic acids, hydrazides, alcohols). The nucleophilic cleavage reaction is both rapid and exceptionally clean in all the cases tested.
引用
收藏
页码:17 / 21
页数:5
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