In peptide synthesis, there are four basic methods to form peptide bonds: enzymatic synthesis, four-component synthesis, amino activation and carboxyl activation. The following is the knowledge about carboxyl activation.
The basic principle of the carboxy activation method
“For NH2R’ to generate RCONHR’ in nucleophilic reaction to be beneficial, the a-carboxyl or N-protected amino acid of the peptide must first be converted to the activated form of RCOX.” In general, the electron-withdrawing property of the substituent group X is positively correlated with its ability to activate the carboxyl group; the more electron-withdrawing property of the substituent group X is, the stronger the latter will be.
Classification of carboxyl activation methods:
It is mainly divided into NCA synthesis method, activated ester method, carbodiimide method and mixed acid anhydride method
1. NCA synthesis method mainly uses phosgene method and acyl chloride method, which has the following advantages:
(1) Except for amino moieties Cys and Lys, the other side chains do not require excessive protection;
(2) faster reaction speed and shorter synthesis period;
(3) able to react in aqueous solution;
(4) The obtained amino free peptide can be directly used in the second round of peptide synthesis reaction.
2. The activated ester method mainly uses DCC method, transesterification reaction, addition and mixed anhydride method
There are five types of solid-phase activated esters, activated amides, alkenyl esters, aryl activated esters, and activated esters formed with N-alkenyl compounds
3, mixed anhydride method: usually in two steps to react
Post time: Dec-18-2024