Synthesis of New Opioid Analgesic Peptide Analogues to Enkephalin (Leucine- and Methionine-Enkephalin)

Muthanna S Al-Ttaee,Ahlam J Qasir,Kawkab Y Saour

doi:10.31351/vol17iss1pp39-46

Abstract

A small number of researches were done in the design and synthesis of enkephalin analogues that are able to resist degradation effect of proteolytic enzymes with good bioavailability and half-lives.Through studying structure activity relationships we tried to incorporate phthalyl group, tryptophan and lysine amino acids in different positions in the basic backbone structure of the naturally occurring opioid Leu5- and Met5- enkephalin, in the hope that such insertion of these amino acids could induce interesting addition in the biological activity of these analogues with enhancement of their bioavailability, in addition to decrease side effects as addiction liability. These synthesized peptides are:  Analogue I: phthalyl-tyrosyl-glycel-tryptophan methyl ester. Analogue II: Boc-tyrosyl-glycyl-phenylalanyl-lysine ethyl ester. HBr.  According to the designed structures, the analogues were synthesized following the conventional solution method and they were identified using the following techniques: melting point, optical rotation, thin layer chromatography (TLC), infrared spectroscopy (IR), elemental analysis (CHN) and amino acid analysis. Key words: peptide, phthalyl, opoioid analgesics

Highlights

The opium group of narcotic drugs is among the most powerfully acting and clinically useful drugs producing depression in the central nervous system (1)
Opioid peptides defined as peptides with opiate-like pharmacological effect (4,5)
The main clinical uses of opioid peptides are as analgesics (7,8), as antioxidants (9), as anticancers (10), as antibacterials and antifungals (11)

Summary

Introduction

The opium group of narcotic drugs is among the most powerfully acting and clinically useful drugs producing depression in the central nervous system (1). Papaveraceae), and include morphine, codeine and a wide variety of semisynthetic congeners derived from them and thebain (another compound of opium) (2). The term opioid is more inclusive, applied to all agonists and antagonists with morphine-like activity as well as to naturally occurring (endogenous) and synthetic opioid peptides (3). Opioid peptides defined as peptides with opiate-like pharmacological effect (4,5). The discovery of endogenous opioids has been followed shortly after the identification of opioid receptors (6). The main clinical uses of opioid peptides are as analgesics (enkephalins) (7,8), as antioxidants (enkephalins) (9), as anticancers (dalargin) (10), as antibacterials and antifungals (phthalyl serine, phthalyl arginine) (11)

Materials and Methods

E: C: Chloroform: Methanol

Results and Discussion