A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex Export

@article{citeulike:3886178, abstract = {10.1158/1535-7163.MCT-05-0456 We show that five topoisomerase I inhibitors (two indenoisoquinolines, two camptothecins, and one indolocarbazole) each intercalate between the base pairs flanking the cleavage site generated during the topoisomerase I catalytic cycle and are further stabilized by a network of hydrogen bonds with topoisomerase I. The interfacial inhibition paradigm described for topoisomerase I inhibitors can be generalized to a variety of natural products that trap macromolecular complexes as they undergo catalytic conformational changes that create hotspots for drug binding. Stabilization of such conformational states results in uncompetitive inhibition and exemplifies the relevance of screening for ligands and drugs that stabilize (\^{a}€œtrap\^{a}€) these macromolecular complexes. [Mol Cancer Ther 2006;5(2):287\^{a}€“95]}, author = {Marchand, Christophe and Antony, Smitha and Kohn, Kurt W. and Cushman, Mark and Ioanoviciu, Alexandra and Staker, Bart L. and Burgin, Alex B. and Stewart, Lance and Pommier, Yves}, citeulike-article-id = {3886178}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1535-7163.MCT-05-0456}, citeulike-linkout-1 = {http://mct.aacrjournals.org/content/5/2/287.abstract}, citeulike-linkout-2 = {http://mct.aacrjournals.org/content/5/2/287.full.pdf}, citeulike-linkout-3 = {http://mct.aacrjournals.org/cgi/content/abstract/5/2/287}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/16505102}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=16505102}, day = {1}, doi = {10.1158/1535-7163.MCT-05-0456}, journal = {Molecular Cancer Therapeutics}, keywords = {inibitors, isoquinoline, topoisomerase}, month = {February}, number = {2}, pages = {287--295}, posted-at = {2009-01-14 18:15:36}, priority = {2}, title = {A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex}, url = {http://dx.doi.org/10.1158/1535-7163.MCT-05-0456}, volume = {5}, year = {2006} }

TY - JOUR ID - citeulike:3886178 L3 - citeulike-article-id:3886178 N2 - 10.1158/1535-7163.MCT-05-0456 We show that five topoisomerase I inhibitors (two indenoisoquinolines, two camptothecins, and one indolocarbazole) each intercalate between the base pairs flanking the cleavage site generated during the topoisomerase I catalytic cycle and are further stabilized by a network of hydrogen bonds with topoisomerase I. The interfacial inhibition paradigm described for topoisomerase I inhibitors can be generalized to a variety of natural products that trap macromolecular complexes as they undergo catalytic conformational changes that create hotspots for drug binding. Stabilization of such conformational states results in uncompetitive inhibition and exemplifies the relevance of screening for ligands and drugs that stabilize (“trap”) these macromolecular complexes. [Mol Cancer Ther 2006;5(2):287–95] IS - 2 JF - Molecular Cancer Therapeutics EP - 295 TI - A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex VL - 5 SP - 287 KW - inibitors KW - isoquinoline KW - topoisomerase AU - Marchand, Christophe AU - Antony, Smitha AU - Kohn, Kurt AU - Cushman, Mark AU - Ioanoviciu, Alexandra AU - Staker, Bart AU - Burgin, Alex AU - Stewart, Lance AU - Pommier, Yves PY - 2006/02/01/ UR - http://dx.doi.org/10.1158/1535-7163.MCT-05-0456 ER -