STRUCTURAL STUDY OF ELECTROLYSIS-INDUCED DEGRADATION OF THE GROWTH-HORMONE RELEASING PEPTIDE HIS-D-TRP-ALA-TRP-D-PHE-LYS-NH2

Growth hormone releasing peptide (GHRP, sequence His-D-Trp-Ala-Trp-D-P he-Lys-NH2) is a synthetic hexapeptide under consideration for transde rmal iontophoretic drug delivery. Cyclic voltammetry, controlled-poten tial electrolysis, HPLC/UV analysis, LC/MS/MS analysis, and EPR spin-t rapping studies indicate that the electrolysis-induced oxidative degra dation of GHRP is likely to be mediated by electrogenerated oxygen rad icals from the electrolysis of water, Within 2 h and up to 2.5 V versu s an Ag/AgCl reference electrode, the peptide backbone remains largely intact The chemical modifications are selectively on imidazole (histi dine) and indole (tryptophan), Strategies for alleviating the electrol ysis-induced degradation of GHRP are proposed.