EDC·HCl and Potassium Salts of Oxyma and Oxyma-B as Superior Coupling Cocktails for Peptide Synthesis.

Nowadays, DIC is the most widely used carbodiimide for solid-phase peptide synthesis, while EDC ·HCl is mostly used only for solution-phase synthesis. In this paper, we report new coupling cocktails containing EDC ·HCl in combination with potassium salts of OxymaPure and Oxyma-B (i.e., K-Oxyma and K-Oxyma-B, respectively). These reagent cocktails gave spectacular purity compared to DIC/classical N-hydroxylamine derivatives in the solid-phase peptide synthesis of the Aib-enkephaline (Aib = 2-aminoisobutyric acid) pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH₂), a hindered peptide. Furthermore, we found that the EDC ·HCl/K-Oxyma combination can be used with DMF, THF, or MeCN as the solvent. The optimized cocktail gave less racemization than benzotriazole derivatives, but slightly more than OxymaPure and Oxyma-B during stepwise solution-phase peptide synthesis. [ABSTRACT FROM AUTHOR]