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• W2901408090 abstract "Overexpression of gonadotropin‐releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [ d ‐Cys 6 , desGly 10 , Pro 9 ‐NH 2 ]‐GnRH, [ d ‐Cys 6 , desGly 10 , Pro 9 ‐NHEt]‐GnRH, and [ d ‐Cys 6 , α‐aza‐Gly 10 ‐NH 2 ]‐GnRH were conjugated with doxorubicin (Dox), respectively, through N‐succinimidyl‐3‐maleimidopropionate as a linker to afford three new GnRH‐Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP‐HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor‐positive MCF‐7 human breast cancer cell line by MTT assay. The three GnRH‐Dox conjugates showed improved metabolic stability in human serum in comparison with AN‐152. The antiproliferative effect of conjugate II ([ d ‐Cys 6 , desGly 10 , Pro 9 ‐NHEt]‐GnRH‐Dox) on MCF‐7 cells was higher than that of conjugate I ([ d ‐Cys 6 , desGly 10 , Pro 9 ‐NH 2 ]‐GnRH‐Dox) and conjugate III ([ d ‐Cys 6 , α‐aza‐Gly 10 ‐NH 2 ]‐GnRH‐Dox), and the cytotoxicity of conjugate II against GnRH receptor‐negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [ d ‐Cys 6 ‐des‐Gly 10 ‐Pro 9 ‐NHEt]‐GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [ d ‐Cys 6 ‐des‐Gly 10 ‐Pro 9 ‐NHEt]‐GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors." @default.
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• W2901408090 date "2018-11-22" @default.
• W2901408090 modified "2023-10-17" @default.
• W2901408090 title "Synthesis, in vitro stability, and antiproliferative effect of <scp>d</scp>‐cysteine modified GnRH‐doxorubicin conjugates" @default.
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• W2901408090 doi "https://doi.org/10.1002/psc.3135" @default.
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