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Influences of Hydrocarbon Linkers on the Receptor Binding Affinities of Gonadotropin-releasing Hormone Peptides

Overview
Journal Bioorg Med Chem Lett
Specialty Biochemistry
Date 2013 Sep 11
PMID 24018188
Citations 5
Authors
Haixun Guo
Helen Hathaway
Melanie E Royce
Eric R Prossnitz
Yubin Miao
Affiliations
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Abstract

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. (111)In-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.

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