SYNTHETIC PEPTIDES AS STRUCTURAL PROBES FOR PRECLINICAL

近二十年来，国家药物滥用研究所一直在提供 致力于解决药物滥用问题的科学界， 规范受控研究药品和化学品的供应。这些 包括大麻香烟，已知的致幻剂，海洛因，安非他命， 大麻素，以及许多其他对临床和治疗至关重要的药物 实验室研究。最近，亮氨酸脑啡肽的分离， Met5-脑啡肽和其他阿片肽产生了一种爆炸性的 对这一研究领域的兴趣。在这些发现之后，证据是 呈现为存在多个受体群体。这些 令人兴奋的发现吸引了一大批科学家，如医学 化学家，药理学家，生物化学家，临床医生，行为科学家， 分子生物物理学家和神经内分泌学家等。 研究已经产生了对几种纯阿片肽的大量需求 支持的一些临床前和临床研究的数量 NIDA--受体结合研究、成瘾评价和镇痛剂 C.D.的潜能、药代动力学和构象研究； X-射线、激光拉曼、傅立叶变换红外光谱等研究阿片肽及其活性 各自的中间体化合物价格昂贵，纯度并不总是很高 充分的，成熟的。在商业上，可用的多肽是 采用固相法合成，不易结晶。 然而，用传统方法合成的多肽更适合于 用于x射线晶体研究，因为它们通常是纯的和 水晶般的。为了提供纯晶型阿片肽 NIDA的研究人员支持的研究，NIDA打算保持 盘点了大约20个多肽及其中间体。通过这件事 合同NIDA计划提供化学纯、无外消旋的多肽 主要是向NIDA受赠者提供资金，同时保持以下能力 按需快速合成潜在有用的新化合物。

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.