INVESTIGATION OF INTERACTIONS BETWEEN DERMORPHIN ANALOGS AND µ-OPIOID RECEPTOR

Abstract

Opioid receptors play the pain control function in the body. Most of the research is carried out to find the most effective analgesic. The earliest analgesic is morphine, however, unfortunately it has many side effects [Mizoguchi H et al. 2003 J. Pharmacol Sci. 93 423]. At a later time dermorphin was discovered as another potent analgesic [Montecucchi P C et al. 1981 Int. J. Pept. Protein Res. 17 275]. Unfortunately, this peptide is not resistant to enzymatic metabolism [Kisara K et al. 1986 Br. J. Pharmacol. 87 183; Sasaki Y et al. 1985 Neuropeptides 5 391]. The objective of this study is to search for new opioid analgesics by investigation of interactions between dermorphin analogs and the µ-opioid receptor using molecular modeling methods. MOPR (µ-Opioid Peptide Receptor) complexes with several ligands (with known biological activity) were modeled to explain how the structure of the complex was related to the biological activity. The investigated dermorphin analogs containing [DMT1, D-Arg2] (especially tetrapeptides) may become a good alternative for the currently used analgesics.

Keywords

• molecular modeling
• opioid receptors
• defmorphin
• molecular docking
• drug design