SYNTHESIS OF ADENOSINE MET-ENKAPHALIN CONJUGATE WITH EXPECTED BIOLOGICAL ACTIVITY

In an effort for designing analogue with improved analgesic activity(opioid like activity) or may posses added biological activities as antimetabolite with antineoplastic antibacterial and antiviral, etc., coupled bi natural metabolites (nucleoside peptides) are proposed in this study to synthesize 1′-deoxy-1′-(6-amino-9-purinyl)-2′,3′-o-isopropylidene-B-D-ribfuranuronic acid amide with TyrGly-Gly-Phe-Met-oH. In the hope that such combination have efficient transporting system across membrane, natural penetration inside the cell and nucleus, represent an essential criteria for specifically inducing the analagesic, antiviral, anticancer and also help for exploring other expected biological activities. The analogue was synthesized by applying the conventional solution method and the coupling between peptide and nucleoside adenosine was carried out through amide linkage.Confirmity of the synthetic procedure was achieved by applying different physico-chemical analyses including, thin layer chromatography (T.L.C) and melting point (M.P.), infrared spectroscopy (IR),elemental analysis(CHN analysis), optical rotation, amino acid analysis and NMR. Keyword: Adenosine, met-Enkaphaline analogue. Introduction Opioid is a chemical substance that has a morphine-like action in the body. The main use is for pain relief. These agents work by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract. The centeral Analgesic activity is mediated by opiate receptors located in the CNS. Five major categories of opioid receptors are known: mu (μ), kappa (κ), sigma (σ), delta (δ), and epsilon (ε). Narcotic. [met]-enkephalin is widely distributed in the CNS; [met]enkephalin is a product of the proenkephalin gene, and acts through μ and δ-opioid receptors. [leu]-enkephalin, also a product of the proenkephalin gene, acts through δ-opioid receptors. The discovery of enkephalins (Hughes 1975) created a new era in which peptides emerged as a novel class of potent analgesics. Soon after their isolation and characterization was reported, the search for other endogenous peptides possessing opioid activity was further intensified and several of them could be isolated from different mammalian tissues and fluids within a short span of time. Almost simultaneously, structure-activity relationship studies on these pentapeptides were undertaken in a number of laboratories, primarily with the object of getting a synthetic peptide that could be utilized as a pain reliever in clinical practice. Adenosine is a nucleoside composed of a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety via a β-N9-glycosidic bond. Adenosine plays an important role in biochemical processes, such as energy transfer-as adenosine triphosphate (ATP) and adenosine diphosphate (ADP) as well as in signal transduction as cyclic adenosine monophosphate, cAMP. It is also an inhibitory neurotransmitter, believed to play a role in promoting sleep and suppressing arousal, with levels increasing with each hour an organism is awake. Because of its simple structure there has been an enomrous amount of interest in development of analogues as medicinal agents. Thousands opioid analogues have been synthesized and studied in an attempt to evaluate their structure activity relationship. Peptide nucleic acids are oligonucleotide mimics characterised by high chemical and enzymatic stability, high specificity and affinity toward complementary DNA/RNA.