SYNTHETIC PEPTIDES AS STRUCTURAL PROBES

合成肽作为结构探针

• 批准号: 2420210
• 负责人: GEORGE A BRINE
• 金额: $ 32.5万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-03-31 至 1998-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2420210
• 关键词: X ray crystallography; chemical structure function; conformation; drug design /synthesis /production; endogenous opioid; opioid receptor; peptide analog; receptor binding; synthetic peptide

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.

脑啡肽的分离产生了阿片肽的希望 或相关化合物可能为开发有用的 治疗鸦片成瘾的药物。它已经被反复地 证明了阿片类物质的三维结构对 在管理它们的生物活动方面发挥关键作用。的第一步 受体特异性和受体亚型特异性配体的设计，以及 新药，是活性化合物的构象分析。X射线 多肽的结晶学和相关构象研究将 帮助推断三维构象和这些方法 提供有关分子结构的最可靠信息。通过 将X射线数据与物理化学数据、理论分析数据、 以及来自生化和药理学研究的数据，设计新的 具有特定生物学特性的配体和新药 可行。目前，大量的构象受到限制 不同的研究实验室已经合成了多肽类药物， 其中一些化合物具有非常高的受体 具体细节。这些都是阐明的理想分子 各种有趣的生物活动的分子决定因素。 尽管人们对X射线结晶学研究有高度的兴趣， 由于石油价格高企，这方面的进展非常有限。 多肽被放在首位，晶体的可用性不足 产品在第二位。为了提供纯净晶状的阿片类药物 NIDA为研究人员提供的多肽支持的研究，NIDA计划保持 大约10-15个多肽及其中间体的清单。穿过 这份合同NIDA计划提供化学纯的，不消旋的 主要向NIDA受赠者提供多肽，同时保持 能够按需快速合成新的配体或新的 必要时用药。总之，这份合同提供了 对药物滥用研究人员有价值的研究化学品。