Effect of reductive alkylation of lysine in positions 6 and/or 8 on the histamine-releasing activity of luteinizing hormone-releasing hormone antagonists.
Effect of reductive alkylation of lysine in positions 6 and/or 8 on the histamine-releasing activity of luteinizing hormone-releasing hormone antagonists.
复制标题
6位和/或8位赖氨酸的还原烷基化对黄体生成素释放激素拮抗剂的组胺释放活性的影响。
DOI：
10.1021/jm00393a038
复制
发表时间：
1987
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 solid-phase reductive alkylation of the Lys side chainin positions 6 (d) and 8 (l) and position 8 alone of the LH-RH antagonist [JV-Ac-D-Nal1, D-Ph2, 3, D-Arg6, Phe7, D-Ala10] LH-RH was investigated in an attempt toreduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovulatory activity. The protected parent analogues were prepared by conventional solid-phase peptide synthesis. After selective removal of the Lys Fmoc side chain protection, the resin-bound peptides were readily and conveniently alkylated at the e amino groups with various aldehydes and ketones in the presence of NaBHgCN. The analogues were then cleaved from the resin with simultaneous deprotection by anhydrous hydrogen fluoride and purified to homogeneity in two stages: gel permeation followed by preparative reversed-phase liquid chromatography. The analogues were assayed in standard rat antiovulatory and in vitro histamine-release assays.
