Novel Techniques for the Solution and Solid Phase Synthesis of Peptide Segments

这项研究的重点是开发普遍适用的，可靠的和快速的程序，用于化学合成较长的肽和小蛋白质（掺入氨基酸75-100或更高的范围）。将对分段缩合和逐步方法进行平行研究，以期最终详细说明后一种技术，以便快速合成高纯度产品，而无需进行精心纯化。重点介绍了基于FMOC氨基酸氟化物和1-羟基-7-偶氮苯并三唑（HOAt）的新型偶联技术。由于邻基效应，后者提供了偶联双保护的氨基酸和肽段而不进行外消旋化的机会。稳定的FMOC保护的氨基酸氟化物衍生物将用于组氨酸和精氨酸。 当全系列的酰基氟化物可用时，将检查29-、41-和76-氨基酸肽的模型合成作为新方法学的测试。相同的模型将通过HOAt衍生的试剂使用逐步和分段偶联方案组装。 有了这个奖项，合成有机计划正在支持博士路易斯A。马萨诸塞州阿默斯特大学化学系的卡皮诺说。Carpino教授将专注于开发普遍适用的，可靠的和快速的化学合成长肽和小蛋白质的程序。将对片段缩合和逐步方法进行平行研究，以期最终详细说明后一种技术，使其能够快速合成高纯度产品，而无需进行繁琐的纯化。随着高级肽在药物化学、药物发现和材料科学领域中的使用越来越多，需要快速、可靠的化学合成高级肽的方法。

The focus of this research is the development of generally applicable, reliable and rapid procedures for the chemical synthesis of longer peptides and small proteins (range of incorporated amino acids 75-100 or higher). Parallel studies of the segment condensations and stepwise approaches will be undertaken with a view to eventual elaboration of the latter technique to allow the quick synthesis of products of high purity without the need for elaborate purification. Promising new coupling techniques based on FMOC amino acid fluorides and 1-hydroxy-7-azobenzotriazole (HOAt) will be emphasized. Because of neighboring group effects, the latter offers the opportunity of coupling both urethane-protected amino acids and peptide segments wthout racemization. Stable FMOC-protected amino acid fluoride derivatives will be made for histidine and arginine. When the full range of acid fluorides is available, model syntheses of 29-, 41- and 76-amino acid peptides will be examined as tests of the new methodolgy. The same models will be assembled via HOAt-derived reagents using both stepwise and segment coupling protocols. %%% With this award, the Synthetic Organic Program is supporting the research of Dr. Louis A. Carpino of the Department of Chemistry at the University of Massachusetts Amherst. Professor Carpino will focus his work on the development of generally applicable, reliable and rapid procedures for the chemical synthesis of longer peptides and small proteins. Parallel studies of the segment condensation and stepwise approaches will be undertaken with the view to eventual elaboration of the latter technique to allow the rapid synthesis of products of high purity without the need for tedious purification. Quick, reliable methods for the chemical synthesis of higher peptides are needed in connection with the increasing use of such substances in the fields of medicinal chemistry, drug discovery and material science.