Conformation and biological studies of synthesized Trp4-Met5 enkephalin N-protected with 3,5-dimethoxy-alpha,...

A highly purified Trp4-Met5 enkephalin was synthesized using liquid phase method of peptide synthesis. Polyethylene glycol (PEG) ans 3,5-dimethoxy-alpha, alpha-dimethylbenzoylcarbonyl group (Ddz) were used as blocking groups for C- and N-terminals, respectively. Ddz group proved to be the suitable N-protecting group for tryptophan-containing peptide. Its acid sensitivity permits mild cleavage without damage to tryptophan. Attachment of methionine with PEG was catalyzed by 18-crown-6. This raised the yield of incorporation from 36 to 98%. Morphine like activity of the prepared peptide was tested by injection into the lateral brain ventricle of the rat. It has a highly biological potency. Conformational studies in solution by CD, energy transfer and in solid state by IR spectroscopy indicated that Trp4-Met5 enkephalin adopts a beta-turn conformation. The intramolecular distance between Tyr and Trp was 11.6 A.