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

点击翻译按钮获取中文摘要

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.