應用不同方式的硫醚鍵架橋反應合成環狀胜?

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Title:	應用不同方式的硫醚鍵架橋反應合成環狀胜?
Other Titles:	Application of different thioether-bridged reactions in the synthesis of cyclic peptides
Authors:	宋飛儀 Sung, Fei-I
Contributors:	龍鳳娣 Lung, Feng-Di 東海大學化學系
Keywords:	固相胜?合成法;環狀胜?
Date:	2008
Issue Date:	2011-03-23T06:09:17Z (UTC)
Abstract:	環狀胜?在生醫研究方面對於藥物開發以及分子探測器來說是很重要的化合物。與線狀胜?做比較，環狀胜?較具功效，因為可以降低構形的自由度，因此比較不會被蛋白質水解?水解，且可以對巨大的分子受體做專一性有效的結合。由於相同種類的含有硫之線性胜?有很高的傾向形成寡聚物，因此分子內的胜?形成反應是形成硫醚鍵方式環狀胜?的關鍵步驟。液相方式的環化反應通常在相當高稀釋溶液的條件下進行環化反應以避免同序列的線狀胜?形成寡聚物。可是，液相的環化反應方法即使在相當高稀釋的條件下也有許多的缺點，如:產生雙聚物和寡聚物類的副反應。將胜?依附在固相支持物上進行環化反應，將能得到類似稀釋現象的效果，使反應傾向於在樹脂上進行胜?分子內的反應，並使分子之間的作用力減到最小。因此硫醚鍵方式的環狀胜?可以藉由固相胜?合成法及依附在樹脂上的環化方法有效的合成出來。本篇研究利用不同的方式來合成硫醚鍵方式的環狀胜?並分析其合成效率以及產率。液相以及固相方式的產率分別為13.76%、17.25%。 Cyclic peptides are significant compounds for drug discovery and molecular probes in biomedical research. Compared to linear peptides, cyclic peptides were generally more effective than the corresponding linear peptides, that have reduced conformational freedom, which makes them more resistant to proteolytic degradation and potentially tighter-binding and more-specific ligands of macromolecular receptors. Intramolecular peptide forming reaction, is the key step in the synthesis of constrained thioether-bridged cyclopeptides due to the high tendency of the corresponding linear peptides to oligomerize. Solution phase cyclization generally react in solution under high dilution conditions to avoid corresponding linear peptides to oligomerize. However, solution-phase methodologies, even in high dilution conditions, suffer from several drawbacks, such as dimerization and oligomerization side reactions. If the peptide remains anchored on a solid support, the cyclization takes advantage of the pseudodilution phenomenon, which favors intramolecular resin-bound reactions, minimizing interchain interactions. Therefore, thioether-bridged cyclopeptides can be conveniently synthesized by SPPS and on-resin cyclization methods. In this study, thioether-bridged cyclopeptides synthesis were performed via different mode (by solution-phase cyclization and on-resin cyclization).The efficiency and yield of both reactions were analyzed. The yields of solution-phase cyclization and on-resin cyclization methods are 13.76% and 17.25%, respectively.
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