Abstract
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.
Original language | English (US) |
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Pages (from-to) | 17-21 |
Number of pages | 5 |
Journal | Letters in Peptide Science |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Biochemistry
Keywords
- C-terminal modified peptides
- Hydrazides
- Hydroxamates
- Multidetachable resin
- Solid-phase peptide synthesis
- Thioester handle