{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:49:42Z","timestamp":1767847782933,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T00:00:00Z","timestamp":1542844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003482","name":"Department of Education of Hebei Province","doi-asserted-by":"publisher","award":["BJ2017055"],"award-info":[{"award-number":["BJ2017055"]}],"id":[{"id":"10.13039\/501100003482","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2017406022"],"award-info":[{"award-number":["H2017406022"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007409","name":"Chengde Medical University","doi-asserted-by":"publisher","award":["201721"],"award-info":[{"award-number":["201721"]}],"id":[{"id":"10.13039\/501100007409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003482","name":"Department of Education of Hebei Province","doi-asserted-by":"publisher","award":["[2013]4"],"award-info":[{"award-number":["[2013]4"]}],"id":[{"id":"10.13039\/501100003482","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Overexpression of gonadotropin\u2010releasing 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 [<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, desGly<jats:sup>10<\/jats:sup>, Pro<jats:sup>9<\/jats:sup>\u2010NH<jats:sub>2<\/jats:sub>]\u2010GnRH, [<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, desGly<jats:sup>10<\/jats:sup>, Pro<jats:sup>9<\/jats:sup>\u2010NHEt]\u2010GnRH, and [<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, \u03b1\u2010aza\u2010Gly<jats:sup>10<\/jats:sup>\u2010NH<jats:sub>2<\/jats:sub>]\u2010GnRH were conjugated with doxorubicin (Dox), respectively, through N\u2010succinimidyl\u20103\u2010maleimidopropionate as a linker to afford three new GnRH\u2010Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP\u2010HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor\u2010positive MCF\u20107 human breast cancer cell line by MTT assay. The three GnRH\u2010Dox conjugates showed improved metabolic stability in human serum in comparison with AN\u2010152. The antiproliferative effect of conjugate II ([<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, desGly<jats:sup>10<\/jats:sup>, Pro<jats:sup>9<\/jats:sup>\u2010NHEt]\u2010GnRH\u2010Dox) on MCF\u20107 cells was higher than that of conjugate I ([<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, desGly<jats:sup>10<\/jats:sup>, Pro<jats:sup>9<\/jats:sup>\u2010NH<jats:sub>2<\/jats:sub>]\u2010GnRH\u2010Dox) and conjugate III ([<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>, \u03b1\u2010aza\u2010Gly<jats:sup>10<\/jats:sup>\u2010NH<jats:sub>2<\/jats:sub>]\u2010GnRH\u2010Dox), and the cytotoxicity of conjugate II against GnRH receptor\u2010negative 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 [<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>\u2010des\u2010Gly<jats:sup>10<\/jats:sup>\u2010Pro<jats:sup>9<\/jats:sup>\u2010NHEt]\u2010GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [<jats:sc>d<\/jats:sc>\u2010Cys<jats:sup>6<\/jats:sup>\u2010des\u2010Gly<jats:sup>10<\/jats:sup>\u2010Pro<jats:sup>9<\/jats:sup>\u2010NHEt]\u2010GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors.<\/jats:p>","DOI":"10.1002\/psc.3135","type":"journal-article","created":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T09:17:34Z","timestamp":1542964654000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synthesis, in vitro stability, and antiproliferative effect of <scp>d<\/scp>\u2010cysteine modified GnRH\u2010doxorubicin conjugates"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9924-5686","authenticated-orcid":false,"given":"Songtao","family":"Li","sequence":"first","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Immunology Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Third Department of Surgery Affiliated Hospital of Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifeng","family":"Yin","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Mao","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhua","family":"Deng","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Hao","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huina","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine Chengde Medical University  Chengde Hebei 067000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2992093"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.11.7087"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.119633"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00777"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(71)80019-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.10.018"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-7-1-44"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1993.tb00495.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1530\/ror.0.0020113"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(72)90490-1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.18.2.0295"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(03)00209-8"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504274102"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.098855"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm8009973"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp4003688"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2014.1697"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc500081g"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1375-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4PY01403K"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.06.052"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2011.05.072"},{"key":"e_1_2_6_24_1","first-page":"1613","article-title":"Enhancing cellular uptake of activable cell\u2010penetrating peptide\u2010doxorubicin conjugate by enzymatic cleavage","volume":"7","author":"Shi NQ","year":"2012","journal-title":"Int J Nanomedicine"},{"key":"e_1_2_6_25_1","first-page":"1806","article-title":"Synthesis of buserelin","volume":"15","author":"Dai T","year":"2014","journal-title":"Chinese J New Drugs"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.829"}],"container-title":["Journal of Peptide Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpsc.3135","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psc.3135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:24:18Z","timestamp":1694777058000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/psc.3135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,22]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/psc.3135"],"URL":"https:\/\/doi.org\/10.1002\/psc.3135","archive":["Portico"],"relation":{},"ISSN":["1075-2617","1099-1387"],"issn-type":[{"value":"1075-2617","type":"print"},{"value":"1099-1387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,22]]},"assertion":[{"value":"2018-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3135"}}