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.
Keywords:
GnRH receptor binding affinity; Gonadotropin-releasing hormone peptide; Hydrocarbon linker.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Aminocaproates / chemistry
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Animals
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Caprylates / chemistry
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Cell Line, Tumor
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Fatty Acids / chemistry
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Female
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Gonadotropin-Releasing Hormone / chemistry
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Gonadotropin-Releasing Hormone / metabolism*
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Heterocyclic Compounds, 1-Ring / chemistry
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Humans
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Hydrocarbons / chemistry*
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Mice
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Mice, Nude
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Peptides / chemical synthesis
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Peptides / metabolism*
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Peptides / urine
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Protein Binding
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Receptors, LHRH / metabolism
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Tissue Distribution
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Transplantation, Heterologous
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gamma-Aminobutyric Acid / chemistry
Substances
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Aminocaproates
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Caprylates
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Fatty Acids
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Heterocyclic Compounds, 1-Ring
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Hydrocarbons
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Peptides
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Receptors, LHRH
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undecanoic acid
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1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
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Gonadotropin-Releasing Hormone
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gamma-Aminobutyric Acid
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octanoic acid