SYNTHETIC PEPTIDES AS STRUCTURAL PROBES

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Isolation of enkephalins has generated the hope that the opioid peptides or related compounds may provide the basis for the development of useful drugs for the treatment of opiate addiction. It has been repeatedly demonstrated that the three dimensional structure of opioids plays a critical role in governing their biological activities. The first step in the design of receptor specific and receptor subtype specific ligands, and new medications, is conformational analyses of active compounds. X-ray crystallographic and related conformational studies of the peptides will help to deduce the three dimensional conformation and these methods provide the most reliable information on molecular structure. By combining X-ray data with physicochemical data, theoretical analysis data, and data from biochemical and pharmacological studies, design of new ligands and new medications with specific biological properties is feasible. At present, a large number of conformationally restricted peptidomimetics have been synthesized by various research laboratories, and some of these compounds have exceptionally high receptor specificities. These serve as ideal molecules for the elucidation of molecular determinants for various interesting biological activities. Despite a high degree of interest in X-ray crystallographic studies, progress in this area has been very limited due to the high price of peptides in the first place, and lack of availability of crystalline products in the second. In order to provide pure and crystalline opioid peptides to researchers for NIDA supported studies, NIDA plans to maintain an inventory of about 10-15 peptides and their intermediates. Through this contract NIDA plans to supply chemically pure, racemization-free peptides primarily to NIDA grantees and at the same time maintain capability to rapidly synthesize, on demand, new ligands or new medications as the necessity arises. In summary, this contract provides valuable research chemicals for drug abuse researchers.