SYNTHETIC PEPTIDES AS STRUCTURAL PROBES

合成肽作为结构探针

• 批准号: 2306329
• 负责人: GEORGE A BRINE
• 金额: $ 46.25万
• 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/2306329
• 关键词: SYNTHETIC; PEPTIDES; STRUCTURAL; PROBES

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希望， 或相关化合物可以为开发有用的 治疗鸦片成瘾的药物。 屡遭 表明阿片类药物的三维结构起着重要作用。 在控制其生物活动中起着关键作用。 的第一步 受体特异性和受体亚型特异性配体的设计，和 新药物，是活性化合物的构象分析。 x射线 肽的晶体学和相关构象研究将 有助于推断三维构象，这些方法 提供分子结构的最可靠信息。 通过 将X射线数据与理化数据、理论分析数据相结合， 以及来自生物化学和药理学研究的数据， 配体和具有特定生物学特性的新药物， 可行 目前，大量构象受限的 肽模拟物已经由各种研究实验室合成， 其中一些化合物有非常高的 特殊性 这些作为理想的分子，用于阐明 各种有趣的生物活性的分子决定因素。 尽管人们对X射线晶体学研究很感兴趣， 这一领域的进展非常有限，原因是 首先是肽，而且缺乏晶体的可用性 产品在第二。 为了提供纯净的晶体阿片类药物 肽的研究人员为NIDA支持的研究，NIDA计划保持 约10-15种肽及其中间体的库存。 通过 该合同NIDA计划提供化学纯，无外消旋 肽主要是NIDA赠款，同时保持 能够按需快速合成新配体或新的 药物治疗，如有必要。 总之，本合同规定 对药物滥用研究人员来说是有价值的研究化学品。