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

在有机合成计划和数学和物理科学理事会多学科活动办公室的支持下，马萨诸塞大学阿默斯特分校化学系的Louis A. Carpino教授开发了肽和肽段溶液和固相合成的新技术。对于长肽和小蛋白质的合成方法，无论是通过逐步溶液或固相技术，还是通过段缩合方法，都不完全令人满意，因为耦合步骤存在问题，组氨酸和精氨酸残基得不到适当保护或不稳定。Carpino教授探索这些氨基酸的新衍生物，允许它们在自动偶联方案中结合和脱保护。研究了诸如肽键保护和聚乙二醇残基等增溶系统在相对非极性溶剂中为生长中的肽提供良好溶解度的能力，以及通过各种技术对肽段偶联的适用性。然后将优化的技术应用于长肽的合成。随着对多肽各种应用需求的持续增长，包括基础生物和生化现象的研究以及新的医学诊断和治疗剂的开发，需要快速、高效、普遍通用的新技术，理想情况下，需要自动合成多肽。马萨诸塞大学阿默斯特分校化学系的Louis A. Carpino教授在有机合成项目和数学与物理科学理事会多学科活动办公室的支持下，开发了这种技术。他的研究重点是设计合适的构建块，以允许自动顺序构建肽，并开发用于构建肽的新技术。后一种技术的核心是高效地使用固体“支撑”作为肽合成的平台，并通过使用可溶性聚合物材料作为构建支架，将这种固相肽合成的基本前提扩展到有机溶剂中的均相溶液。

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.