Influences of hydrocarbon linkers on the receptor binding affinities of gonadotropin-releasing hormone peptides

被引：10
|
作者：
Guo, Haixun [1 ]
Hathaway, Helen [2 ,3 ]
Royce, Melanie E. [3 ,4 ]
Prossnitz, Eric R. [2 ,3 ]
Miao, Yubin [1 ,3 ,5 ]
机构：
[1] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA
[3] Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA
[4] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA
[5] Univ New Mexico, Dept Dermatol, Albuquerque, NM 87131 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 20期
关键词：
Gonadotropin-releasing hormone peptide; Hydrocarbon linker; GnRH receptor binding affinity; HUMAN-BREAST-CANCER; GROWTH; CELLS; AGONIST; SITES;
D O I：
10.1016/j.bmcl.2013.08.075
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Three new DOTA-conjugated GnRH peptides with various hydrocarbon linkers were synthesized to evaluate the influences of the linkers on their receptor binding affinities. The hydrocarbon linker displayed a profound impact on the receptor binding affinities of DOTA-conjugated GnRH peptides. The Aun linker was better than Gaba, Ahx and Aoc linkers in retaining strong receptor binding affinity of the GnRH peptide. DOTA-Aun-(D-Lys(6)-GnRH) displayed 22.8 nM GnRH receptor binding affinity. In-111-DOTA-Aun-(D-Lys(6)-GnRH) exhibited fast tumor uptake and urinary clearance in MDA-MB-231 human breast cancer-xenografted nude mice. The cellular and biological results provided an insight into the design of new GnRH peptides in the future. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5484 / 5487
页数：4
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