Novel Techniques for the Solution and Solid Phase Syntheses of Peptides and Peptide Segments

在有机合成计划和办公室的支持下， 数学和物理科学的多学科活动 董事会，路易斯·A.卡尔皮诺，化学系 在阿默斯特的马萨诸塞州大学， 用于肽和肽的溶液和固相合成 片段 用于合成较长肽和小肽的方法 蛋白质，无论是通过逐步溶液或固相技术，或通过 段缩合方法，并不完全令人满意，遭受 耦合步骤中的问题以及 适当保护的组氨酸和精氨酸残基。 卡皮诺教授 探索这些氨基酸的新衍生物， 在自动化偶联方案中的掺入和脱保护。 增溶系统，如肽键保护和聚乙烯 乙二醇）残留物检查其提供良好 生长肽在相对非极性溶剂中的溶解度， 由于它们用于通过各种方法偶联肽段的适用性， 技术. 然后将优化的技术应用于合成 长肽 随着对用于多种用途的多肽的需求的持续增长， 应用，包括基础生物学和 生物化学现象和新的医学诊断的发展， 治疗剂，新技术的快速，有效，普遍 需要多肽的一般性和理想的自动化合成。 Louis A.卡尔皮诺，化学系， 马萨诸塞州阿默斯特大学，在有机的支持下， 综合方案和多学科活动办公室 数学和物理科学理事会，开发这种技术。 他的研究既集中在设计合适的积木， 允许肽的自动化顺序构建， 开发新的多肽构建技术。 的 后一种技术集中在固体“支持物”的高效使用上。 作为肽合成的平台，并扩展了 在有机溶剂中均相溶液的固相肽合成 通过使用可溶性聚合物材料作为 建筑脚手架

With the support of the Organic Synthesis Program and the Office of Multidisciplinary Activities of the Mathematical and Physical Sciences Directorate, Professor Louis A. Carpino, of the Department of Chemistry at the University of Massachusetts, Amherst, develops novel techniques for the solution and solid phase synthesis of peptides and peptide segments. Methods for the synthesis of longer peptides and small proteins, whether by stepwise solution or solid phase techniques or by segment condensation methods, are not wholly satisfactory, suffering from problems in the coupling steps and the unavailability or instability of suitably protected histidine and arginine residues. Professor Carpino explores new derivatives of these amino acids, permitting their incorporation and deprotection in automated coupling schemes. Solubilizing systems such as peptide bond protection and poly(ethylene glycol) residues are examined for their ability to provide good solubility of growing peptides in comparatively non-polar solvents and for their applicability for the coupling of peptide segments by various techniques. Optimized techniques are then applied to the synthesis of longer peptides. With continued growth in the demand for polypeptides for a variety of applications, including the study of fundamental biological and biochemical phenomena and the development of new medical diagnostics and therapeutic agents, new techniques for the rapid, efficient, universally general, and, ideally, automated synthesis of polypeptides are required. Professor Louis A. Carpino, of the Department of Chemistry at the University of Massachusetts, Amherst, with the support of the Organic Synthesis Program and the Office of Multidisciplinary Activities of the Mathematical and Physical Sciences Directorate, develops such techniques. His studies focus both on the design of suitable building blocks to allow the automated sequential construction of peptides and on the development of new techniques for the construction of peptides. The latter techniques center on the highly effective use of solid `supports` as platforms for peptide synthesis and extend the basic premises of such solid-phase peptide synthesis to homogeneous solutions in organic solvents through the use of soluble polymeric materials as the construction scaffold.