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RNR inactivation is reductant\u2010dependent and occurs in a very different way from that of other known substrate analogues. In the presence of reductants monomer R1 of RNR is inhibited, whereas in the absence of reductants the radical is lost and monomer R2 is inhibited. As inside the cell reductants are available, it is likely that R1 inactivation is the most favorable mechanism responsible for drug cytotoxicity. This inhibition pathway has been unknown to date, but we have conducted a theoretical study that has led us to the first proposal of a mechanism for RNR inhibition by dFdC in the presence of reductants.<\/jats:p>","DOI":"10.1002\/chem.200700260","type":"journal-article","created":{"date-parts":[[2007,7,18]],"date-time":"2007-07-18T12:23:50Z","timestamp":1184761430000},"page":"8507-8515","source":"Crossref","is-referenced-by-count":121,"title":["Understanding Ribonucleotide Reductase Inactivation by Gemcitabine"],"prefix":"10.1002","volume":"13","author":[{"given":"Nuno\u2005M.\u2005F.\u2005S.\u2005A.","family":"Cerqueira","sequence":"first","affiliation":[]},{"given":"Pedro\u2005A.","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Maria\u2005J.","family":"Ramos","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2007,10,2]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408369709006424"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.18.8403"},{"key":"e_1_2_6_3_2","first-page":"7","volume":"24","author":"Fukuoka M.","year":"1997","journal-title":"Semin. 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