高等学校化学学报

高等学校化学学报 ›› 2013, Vol. 34 ›› Issue (5): 1139.doi: 10.7503/cjcu20130086

• 有机化学 • 上一篇    下一篇

低组胺释放副作用的GnRH拮抗剂的设计合成及活性评价

周宁, 林凡程, 高星, 周文霞, 程军平, 刘克良, 张永祥   

  1. 军事医学科学院毒物药物研究所, 北京 100850
  • 收稿日期:2013-01-24 出版日期:2013-05-10 发布日期:2013-05-10
  • 通讯作者: 刘克良, 男, 博士, 研究员, 博士生导师, 主要从事多肽药物和核酸化学研究. E-mail: keliangliu55@126.com E-mail:keliangliu55@126.com
  • 基金资助:

    国家自然科学基金(批准号: 81172925)资助.

Design, Synthesis and Bioactivity Evaluation of GnRH Antagonists with Low Histamine-releasing Potency

ZHOU Ning, LIN Fan-Cheng, GAO Xing, ZHOU Wen-Xia, CHENG Jun-Ping, LIU Ke-Liang, ZHANG Yong-Xiang   

  1. Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
  • Received:2013-01-24 Online:2013-05-10 Published:2013-05-10
  • Contact: Keliang Liu E-mail:keliangliu55@126.com

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被引次数

1

摘要：

根据肽类组胺释放剂具有多个碱性氨基酸的结构特点, 将具有羧基结构的基团引入促性腺激素释放激素(GnRH)的不同位置, 合成了一系列新的GnRH类似物, 并进行了大鼠体内抑制睾酮释放的生物活性评价及大鼠腹腔肥大细胞中的促组胺释放副作用评价. 结果表明, 某些带有酸性基团的GnRH类似物不仅组胺释放副作用大大降低, 而且保留了原有的生物活性. 该结果为研发具有低组胺释放副作用的安全型GnRH拮抗剂药物提供了新的构效关系信息.

关键词: 组胺释放副作用, 酸性基团, 促性腺激素释放激素

Abstract:

The histamine-releasing potency of gonadotropin-releasing hormone(GnRH) antagonists induced the serious side effect in clinical application. Because the histamine-releasing peptides usually had one or more basic amino acids. Therefore, the carboxyl groups were introduced to the position 6, 8 or N-terminal of GnRH in order to develop the safe GnRH antagonists, and novel GnRH analogues were synthesized. The experimental results showed that some GnRH analogues with carboxyl group not only have low histamine-releasing potency, but also retained intrinsical testesterone-inhibiting bioactivity. It suggested the method of decreasing the histamine-releasing potency of the peptides by introducing the carboxyl groups was feasible.

Key words: Histamine-releasing potency, Carboxyl group, GnRH

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