​​Symmetric Anhydride Method for Polypeptide Synthesis

Peptide Synthesis

Symmetric Anhydride of Nα－alpha-acyl amino acid is an high-activity midbody for peptide bond formation. In contrast to the mixed anhydride method, it has no ambiguous regional selectivity with the reaction of the amine nucleophile. But peptide condensation rate was the highest, which is 50% (in carboxylic components).

Although free Nα－acyl amino acid formed by symmetric anhydride can be extracted and recycled by aturated sodium bicarbonate solution together with target peptides, but at first, the practical value of this method is extremely low. The acid anhydride can be synthesized by using Nα－protected amino acid and phosgene, or the advantageous carbodiimide reaction. Reaction of two equivalent Nα－protected amino acid and equivalent carbodiimide were favorable for the formation of symmetric anhydride. Symmetrical anhydride can be separated, also it can be applied directly to the latter condensation reaction without purification. Based on the Symmetrical anhydride of hydrolysis stability of Nα－alkyl carbonyl amino acid, the similar purification of this method can be carried out.

Due to Boc-protected amino acid's commercialization and reasonable price, the use of symmetric anhydride method has been paid more and more attention to the gradual lengthening of the peptide chain. Although crystalline anhydride can be purchased, in-situ synthesisin is still a right choice.