title: Influences of hydrocarbon linkers on the receptor binding affinities of gonadotropin-releasing hormone peptides.
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.
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Haixun
authors.initials: H
authors.lastname: Guo
authors.forename: Helen
authors.initials: H
authors.lastname: Hathaway
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Royce
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
mesh_terms: D000614:Aminocaproates / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002210:Caprylates / Q000737:chemistry; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000737:chemistry; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000652:urine; D011485:Protein Binding; D011966:Receptors, LHRH / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: D000614:Aminocaproates; D002210:Caprylates; D005227:Fatty Acids; D006573:Heterocyclic Compounds, 1-Ring; D006838:Hydrocarbons; D010455:Peptides; D011966:Receptors, LHRH; C016173:undecanoic acid; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid; C031492:octanoic acid
keywords: GnRH receptor binding affinity; Gonadotropin-releasing hormone peptide; Hydrocarbon linker
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