Improved antagonists of luteinizing hormone-releasing hormone modified in position 7.
Improved antagonists of luteinizing hormone-releasing hormone modified in position 7.
复制标题
7位修饰的黄体生成素释放激素拮抗剂的改进。
DOI：
10.1021/jm00145a022
复制
发表时间：
1985
影响因子：
7.3
通讯作者：
Coy,DH
中科院分区：
文献类型：
--
作者：
Hocart,SJ;Nekola,MV;Coy,DH
The structure-activity relationship of position 7 in the antagonist [N-Ac-D-Nal1, D-pClPhe2, D-Trp3*, D-Arg6, D-Ala10]-LH-RH has been investigated by the incorporation of a series of amino acids at this position. The analogues were prepared by solid-phase peptide synthesis. All purifications were performed in two stages: gel permeation followed by preparative reversed-phase high-performance liquid chromatography. The analogues were assayed in the standard rat antiovulatory assay using a 40% propylene glycol-saline vehicle. The results demonstrated that position 7 requires a hydrophobic aromatic amino acid for greatest antiovulatory activity. The compound [N-Ac-D-Nal1, D-pCIPhe2, D-Trp3, D-Arg6, Phe7, D-Ala10]-LH-RH caused 65% blockade of ovulation at the 500-ng dose and is approximately twice as active as the parent analogue in this assay system. The enhanced activity may indicate the stabilization of the active conformation via intramolecular hydrophobic or— interactions.
