{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:47:20Z","timestamp":1787503640016,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"content-version":"am","delay-in-days":324,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000086","name":"Directorate for Mathematical and Physical Sciences","doi-asserted-by":"publisher","award":["CHE-1152054"],"award-info":[{"award-number":["CHE-1152054"]}],"id":[{"id":"10.13039\/100000086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA014236"],"award-info":[{"award-number":["CA014236"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2018,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A prodrug approach is presented to direct copper\u2010dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by \u03b3\u2010glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its thiol reactivity and metal binding properties. In vitro studies demonstrated successful masking of copper binding as well as clean liberation of the chelator by GGT. GGTDTC was stable to non\u2010specific degradation when incubated with a series of prostate cancer and normal cell lines, with selective release of diethyldithiocarbamate only occurring in cells with measurable GGT activity. The antiproliferative efficacy of the prochelator correlated with cellular GGT activity, with 24\u2005h inhibitory concentrations ranging from 800\u2005n\n                    <jats:sc>m<\/jats:sc>\n                    in prostate cancer lines 22Rv1 and LNCaP to over 15\u2005\u03bc\n                    <jats:sc>m<\/jats:sc>\n                    in normal prostate PWR\u20101E cells. These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal\u2010binding pharmacophore.\n                  <\/jats:p>","DOI":"10.1002\/anie.201807582","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T14:44:40Z","timestamp":1532011480000},"page":"12780-12784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Leveraging \u03b3\u2010Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells"],"prefix":"10.1002","volume":"57","author":[{"given":"Subha","family":"Bakthavatsalam","sequence":"first","affiliation":[{"name":"Duke University Department of Chemistry  POB 90346 Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Sleeper","sequence":"additional","affiliation":[{"name":"Duke University Department of Chemistry  POB 90346 Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azim","family":"Dharani","sequence":"additional","affiliation":[{"name":"Duke University Department of Chemistry  POB 90346 Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"George","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine Duke Cancer Institute  Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-3531","authenticated-orcid":false,"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine Duke Cancer Institute  Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-0998","authenticated-orcid":false,"given":"Katherine J.","family":"Franz","sequence":"additional","affiliation":[{"name":"Duke University Department of Chemistry  POB 90346 Durham 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4045"},{"key":"e_1_2_2_3_2","first-page":"467","volume":"31","author":"Aggarwal R. R.","year":"2017","journal-title":"Oncology"},{"key":"e_1_2_2_4_1","unstructured":"\u00a0"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb400198p"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9245"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7DT01955F"},{"key":"e_1_2_2_8_1","unstructured":"\u00a0"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.195628"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.126979"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-015-0968-4"},{"key":"e_1_2_2_12_2","first-page":"1649","volume":"47","author":"Peng F.","year":"2006","journal-title":"J. Nucl. Med."},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-3527"},{"key":"e_1_2_2_14_1","unstructured":"\u00a0"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005538"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1992.tb03310.x"},{"key":"e_1_2_2_17_1","unstructured":"\u00a0"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm049568z"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4CC04767B"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5TX00210A"},{"key":"e_1_2_2_21_1","unstructured":"\u00a0"},{"key":"e_1_2_2_22_2","first-page":"197","volume":"1","author":"Cen D.","year":"2002","journal-title":"Mol. Cancer Therap."},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27482"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25016"},{"key":"e_1_2_2_25_1","unstructured":"\u00a0"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1035"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.12.014"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2015.02.007"},{"key":"e_1_2_2_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e328334131d"},{"key":"e_1_2_2_30_1","unstructured":"\u00a0"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2014.09.015"},{"key":"e_1_2_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eatbeh.2014.10.008"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7176.185944"},{"key":"e_1_2_2_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-016-0865-z"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2013.28"},{"key":"e_1_2_2_36_1","unstructured":"\u00a0"},{"key":"e_1_2_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-016-0183-z"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2016.08.001"},{"key":"e_1_2_2_39_1","unstructured":"\u00a0"},{"key":"e_1_2_2_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.6b00380"},{"key":"e_1_2_2_41_2","first-page":"0","volume":"0","author":"Zaengle-Barone J. M.","year":"2018","journal-title":"ACS Infect Dis."},{"key":"e_1_2_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.10.004"},{"key":"e_1_2_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201203255"},{"key":"e_1_2_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2017.12.016"},{"key":"e_1_2_2_45_1","unstructured":"\u00a0"},{"key":"e_1_2_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-420117-0.00003-7"},{"key":"e_1_2_2_47_2","first-page":"1169","volume":"30","author":"Corti A.","year":"2010","journal-title":"Anticancer Res."},{"key":"e_1_2_2_48_1","unstructured":"\u00a0"},{"key":"e_1_2_2_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809608200"},{"key":"e_1_2_2_50_2","unstructured":"M.\u2005H. Hanigan T. Macdonald (Ed.: V. The University of Virginia (Charlottesville)) United States 1998;"},{"key":"e_1_2_2_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00181"},{"key":"e_1_2_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03760-3"},{"key":"e_1_2_2_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201702210"},{"key":"e_1_2_2_54_1","unstructured":"\u00a0"},{"key":"e_1_2_2_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00137a001"},{"key":"e_1_2_2_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2014937"},{"key":"e_1_2_2_57_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2mt20069d"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121435"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanie.201807582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201807582","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.201807582","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/anie.201807582","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201807582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T12:44:35Z","timestamp":1694695475000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.201807582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":58,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2018,9,24]]}},"alternative-id":["10.1002\/anie.201807582"],"URL":"https:\/\/doi.org\/10.1002\/anie.201807582","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,29]]},"assertion":[{"value":"2018-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}