Side-reactions in peptide synthesis. 2. Formation of by-products in the large-scale synthesis of THF-gamma 2 by solution synthesis.

Abstract

The impurities which formed in the large-scale synthesis of THF-gamma 2, an immunomodulatory peptide of formula H-Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu-OH, were identified by a combination of analytical methods, and their structure confirmed by synthesis. Most impurities originated from side-reactions involving the aspartyl residue (cyclization, beta-aspartyl formation and cleavage). Based on this knowledge, modifications were introduced into the work up and the purification procedure which resulted in a very pure final product (> 99% by RP-HPLC).