The role of peptide backbone modifications in increasing biological stability of LHRH analogs.
The role of peptide backbone modifications in increasing biological stability of LHRH analogs.
复制标题
肽主链修饰在提高 LHRH 类似物生物稳定性中的作用。
DOI：
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发表时间：
1981
期刊：
影响因子：
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通讯作者：
C. Bowers
中科院分区：
文献类型：
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作者：
A. Spatola;A. L. Bettag;N. Agarwal;H. Saneii;W. Vale;C. Bowers
LHRH的激动剂和拮抗剂类似物用于生育调节的潜在有用性已经知道多年。大多数制备新肽类似物的方法都涉及加强肽骨架或酰胺键中的弱连接。这项研究的作者发起了一项计划，在LHRH及其拮抗剂中引入了几种新的容易合成的酰胺键替代物;这些酰胺键替代物包括以下硫基部分：CH 2S CH 2SO CHCH 3S和CHCH 3SO。一般来说，所有含有phi[CH 2S]连接的LHRH类似物已被证明在体外具有高活性，但在体内作为抗排卵剂无活性。含有phi[CH 2SO]取代的类似物的合成表明，化合物在体外和体内无活性。结合phi [CHCH 3S]连接的手性酰胺键置换类的合成被证明是迄今为止各种基于硫的酰胺键置换中最成功的。许多实验室正在进行许多肽骨架修饰。
The potential usefulness of agonistic and antigonistics analogs of LHRH for fertility regulation has been known for years. Most approaches to the preparation of new peptide analogs have involved the strengthening of the weak link in the peptide backbone or the amide bond. The authors of this study initiated a program that incorporated several new kinds of readily synthesized amide bond replacements within LHRH and its antagonists; these amide bond replacements include the following sulfur-based moieties: CH2S CH2SO CHCH3S and CHCH3SO. In general all of the LHRH analogs containing the phi[CH2S] link have been proven highly active in vitro but inactive as antiovulatory agents in vivo. The synthesis of analogs containing the phi[CH2SO] replacement showed that the compounds were inactive in vitro and in vivo. The synthesis of the class of chiral amide bond replacement incorporating a phi [CHCH3S] link proved to be the most successful of the various sulfur-based amide bond replacements thus far. A number of peptide backbone modifications are ongoing in many laboratories.