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Influences of hydrocarbon linkers on the receptor binding affinities of gonadotropin-releasing hormone peptides |
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| Authors: | Haixun Guo Helen Hathaway Melanie E. Royce Eric R. Prossnitz Yubin Miao |
| Affiliation: | 1. College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA;2. Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM 87131, USA;3. Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA;4. Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA;5. Department of Dermatology, University of New Mexico, Albuquerque, NM 87131, USA |
| 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-Lys6-GnRH) displayed 22.8 nM GnRH receptor binding affinity. 111In-DOTA-Aun-(d-Lys6-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. |
| Keywords: | Gonadotropin-releasing hormone peptide Hydrocarbon linker GnRH receptor binding affinity |
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