Synthesis of Estrone-Opioid Peptide Analogue With Expected Analgesic Activity

Abstract

The search for new peptides to be used as analgesics in place of morphine has been mainly directed to develop peptide analogues to have higher biological stability and receptor selectivity.Therefore extensive researches have been carried out on naturally occurring and synthetic opiates in order to enhance the analgesic potency, so we intended to prepare opioiod peptide analogue linked to estrone which may increase the analgesic effect of this compound. Steric hindrance clearly will be produced by estrone may affect the enzymatic activity on the synthesized analogue and this in turn may enhance the bioavailability of the analogue itself, meanwhile estrone may affect physicochemical properties of the analogue by increasing its lipophilicity and so facilitate its passage through the biological barriers, also estrone may affect receptor binding selectivity of this analogue and decrease the side effect of the original opioid peptide.The designed analogue is (estrone-3-O-acyl-tyr-gly-gly-phe-met-OH), where this opioid peptide synthesized following the conventional solution method, then linked to estrone by amide linkage and it was characterized using: thin layer chromatography (TLC), melting point, infrared spectroscopy (IR), elemental microanalysis(CHN), optical rotation, amino acid analysis, and hydrogen-nuclear magnetic resonance( 1 H-NMR).