SOLUTION PHASE AND SOLID PHASE PEPTIDE SYNTHESIS

合成肽的方法有一个共同点，即保护氨基酸末端 和侧链以帮助指导肽形成。 在肽合成期间， 这些保护基团的性质对于本发明的成功变得至关重要。 合成. 这些保护基中的一些使肽片段不溶 因此限制了合成。 金属离子保护基团被提出来替代和补充其他有机保护基团， 组 金属离子的吸引人的特征包括它们的电荷、颜色和易变性。 的引进和淘汰。 金属离子的正电荷保护 基团可以是手柄，其将显著有助于纯化 在合成过程中的任何阶段合成肽。 动力学惰性金属 离子可以像有机保护基团一样稳定，但可以容易地去除 在非常温和的条件下（通过利用它们的氧化还原性质）。 我们建议使用动力学惰性金属离子，特别是 （（NH3）5Co（III）-）和其他钴（III）衍生物，以帮助肽合成。 可通过多种方式：（a）作为C-和N-末端的保护基;（B）作为 各种氨基酸侧链的保护基;（c）掺入 建议将钴（III）吸附到聚合物载体上，以允许除去钴（III）。 在非常温和的条件下从聚合物载体中分离肽;和最后，（d） 在水溶液中的肽合成的主题是使用这些 水溶性金属离子保护基团，其可以在非常温和的条件下除去， 条件 血管紧张素II，一种八残基多肽，将使用 钴（III）保护基团，以证明这种方法的有用性。

Synthetic peptide methods share in common the protection of amino acid terminals and side chains to help direct peptide formation. During peptide synthesis the properties of these protecting groups become vital to the success of the synthesis. Some of these protecting groups render peptide fragments insoluble and therefore limit the synthesis. Metal ion protecting groups are proposed to replace and complement other organic groups. Attractive features of metal ions include their charge, color, and ease of introduction and removal. The positive charge of the metal ion protecting group can be a handle which will significantly aid in the purification of the synthesized peptide at any stage during the synthesis. Kinetically inert metal ions can be as stable as organic protecting groups, yet can be easily removed under very mild conditions (by making use of their redox properties). We are proposing to use kinetically inert metal ions, especially ((NH3)5Co(III)-) and other cobalt (III) derivatives, to aid peptide synthesis in a variety of ways: (a) as a protecting group for C-and N-terminals; (b) as a protecting group for various amino acid side chains; (c) the incorporation of cobalt(III) onto a polymeric support is suggested to allow the removal of a peptide from the polymeric support under very mild conditions; and finally, (d) the subject of peptide synthesis in aqueous solution is approached using these water soluble metal ion protecting groups which can be removed under very mild conditions. Angiotensin II, an eight residue polypeptide, will be synthesized using cobalt(III) protecting groups to demonstrate the usefulness of this approach.