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.
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页码：5484 / 5487
页数：4
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