Protein Chemistry. Structure, Properties, Research Methods - Shendryk A.N. 2022

Peptide Synthesis
Amino acid racemization in peptide synthesis

The probability of Amino Acid Racemization during Peptide synthesis varies significantly across different Methods. To date, no racemization has been detected when using the azide method.

The $p$-nitrophenyl ester method also shows no racemization under optimal peptide synthesis conditions. Under less favorable conditions, the degree of racemization can reach 20% or more. Racemization of $p$-nitrophenyl esters of $N$-protected Amino Acids occurs particularly easily in alkaline media.

The $N,N’$-dicyclohexylcarbodiimide method—under optimal conditions (Temperature -5°C; free amino esters; non-polar media)—causes practically no racemization. In general, the degree of racemization is heavily influenced by The Nature of the solvent. One of the most unfavorable Solvents in this regard is dimethylformamide, in which room-temperature racemization exceeding 50% has been observed.

The Mixed Anhydride Method utilizing carbonic acid monoesters leads to racemization even under optimal process conditions. The solvent has a significant impact on the degree of racemization.

The phosphorazo method is characterized by a very high degree of racemization, which cannot be reduced even by lowering the reaction temperature.



Last update: 06/08/2026

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