Synthesis of 2-Substituted Enkephalin Derivatives for Analgesic Activity

Endomorphin, enkephalin and dynorphin are the endogenous opioid pentapeptides possessing analgesic properties. They are described as endogenous ligands for the opioid receptors. Enkephalin is the simple pentapeptides and it is existing in two forms: LeuEnkephalin (Tyr-Gly-Gly-Phe-Leu) and MetEnkephalin-(Tyr-Gly-Gly-Phe-Met) [1]. It acts as a natural pain killer and also having fewer side effects compared to other opioid peptides [2]. Apart from analgesic activity, it also possesses antidepressant, antianxiety, anticonvulsant activities [3]. A basic amino terminal of Tyr is essential for the opioid activity of enkephalins and removal of the same results in practically inactive peptide [4]. It is well known from the reference that the most feasible position for modifying the enkephalin is 2 glycine unit and next priority to the 4 position Phe unit.