Structural study of electrolysis-induced degradation of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2

• Published in: Analytical chemistry (Washington) Vol. 67; no. 22; pp. 4053 - 4056
• Main Authors: Cheng, Hung-Yuan, Davis, Louisa L, Huddleston, Michael J, Carr, Stephen A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.11.1995
• Subjects: Amino Acid Sequence; Biochemistry; Biological and medical sciences; Chemistry; Electrochemistry; Electrolysis; Electron Spin Resonance Spectroscopy; Exact sciences and technology; General and physical chemistry; General pharmacology; Growth Hormone-Releasing Hormone - chemistry; Hormones; Kinetics and mechanism of reactions; Mass Spectrometry; Medical sciences; Molecular Sequence Data; Peptides; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Chemical analysis; Peptide hormone; EPR spectrometry; HPLC chromatography; Percutaneous route; Electrodes; Cyclic voltammetry; Iontophoresis; Platinum; Oxidation; Hormone releasing factor; Electrochemical reaction; Organic compounds; Sodium Chlorides; Delivery system; Coupled method; Transition metal; Acetate; Experimental study; Buffer solution; Hexapeptide; Hypothalamic hormone; Synthetic product; Degradation product; Mass spectrometry
• DOI: 10.1021/ac00118a004
• ISSN: 0003-2700

Growth hormone releasing peptide (GHRP, sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide under consideration for transdermal iontophoretic drug delivery. Cyclic voltammetry, controlled-potential electrolysis, HPLC/UV analysis, LC/MS/MS analysis, and EPR spin-trapping studies indicate that the electrolysis-induced oxidative degradation of GHRP is likely to be mediated by electrogenerated oxygen radicals from the electrolysis of water. Within 2 h and up to 2.5 V versus an Ag/AgCl reference electrode, the peptide backbone remains largely intact. The chemical modifications are selectively on imidazole (histidine) and indole (tryptophan). Strategies for alleviating the electrolysis-induced degradation of GHRP are proposed.