SYNTHETIC PEPTIDES AS STRUCTURAL PROBES FOR PRECLINICAL

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For nearly two decades, the National Institute on Drug Abuse has provided the scientific community working on problems of drug abuse with authentic, standardize supplied of controlled research drugs and chemicals. These include marijuana cigarettes, known hallucinogens, heroin, amphetamines, cannabinoids, and many other drugs essential for both clinical and laboratory research studies. Recently, the isolation of Leu5-enkephalin, Met5-enkephalin and other opioid peptides has generated an explosive interest in this research area. Following these discoveries, evidence was presented for the existence of multiple populations of receptors. These exciting discoveries attracted a host of scientists such as medicinal chemists, pharmacologists, biochemists, clinicians, behavioral scientists, molecular biophysicists, and neuroendocrinologists, etc. This active research has generated the need for several pure opioid peptides in large quantities for a number of preclinical and clinical studies supported by NIDA--receptor binding studies, evaluation of addiction and analgetic potential, pharmacokinetics studies, and conformation studies by C.D.; N.M.R.; X-ray, laser-Raman, FT-IR, etc. Opioid peptides and their respective intermediates compounds are expensive and purity is not always sufficiently, established. Commercially, available peptides are synthesized by solid phase method and are difficult to crystallize. However, peptides synthesized by the conventional method are more suitable for x-ray crystallographic studies since they are usually pure and crystalline. In order to provide pure crystalline opioid peptides to researchers for NIDA supported studies, NIDA intends to maintain an inventory of about 20 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 compounds that are potentially, useful.