SYNTHETIC PEPTIDES AS STRUCTURAL PROBES FOR PRECLINICAL

合成肽作为临床前结构探针

• 批准号: 6031429
• 负责人: GEORGE A BRINE
• 金额: $ 39.25万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-31 至 2003-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031429
• 关键词: drug design /synthesis /production; endogenous opioid; synthetic peptide

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.

近二十年来，国家药物滥用研究所提供了 致力于解决药物滥用问题的科学界， 管制研究药物和化学品标准化供应。这些 包括大麻香烟、已知致幻剂、海洛因、安非他明 大麻素和许多其他药物对临床和 实验室研究。最近，Leu 5-脑啡肽的分离， Met 5-脑啡肽和其他阿片肽产生了爆炸性的 对这个研究领域感兴趣。在这些发现之后， 提出了多个群体的受体的存在。这些 令人兴奋的发现吸引了一大批科学家， 化学家，药理学家，生物化学家，临床医生，行为科学家， 分子生物药理学家和神经内分泌学家等。 研究已经产生了对几种大规模纯阿片肽的需求 支持的大量临床前和临床研究的数量 NIDA-受体结合研究，成瘾和戒毒评估 C.D.进行的电位、药代动力学研究和构象研究; N.M.R.; X射线、激光拉曼、红外光谱等。 相应的中间体化合物是昂贵的，并且纯度并不总是 充分，建立。市售的肽是 采用固相法合成，不易结晶。 然而，通过常规方法合成的肽更合适 用于X射线晶体学研究，因为它们通常是纯的， 结晶的为了提供纯的结晶阿片肽， 研究人员为NIDA支持的研究，NIDA打算保持一个 约20种肽及其中间体的库存。通过这个 合同NIDA计划提供化学纯，无消旋肽 主要是向NIDA赠款人提供，同时保持能力， 根据需要快速合成潜在有用的新化合物。