By Val R. Adams
ISBN-10: 1588290271
ISBN-13: 9781588290274
A serious assessment our present realizing of camptothecins, their shortcomings, and of the probabilities for bettering their medical functionality. The authors talk about new camptothecin analog improvement, drug supply concerns for optimizing their anticancer job, and their strength use in quite a few various cancers. extra chapters describe what's identified concerning the biochemistry, the pharmacology, and the chemistry of the camptothecins, together with the mechanism of topoisomerase and the way camptothecins poison this enzyme, using animal versions in defining the anticancer strength of camptothecins, and the query of camptothecin resistance.
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Additional info for Camptothecins in Cancer Therapy
Example text
Three protein contacts stabilize the open form of the intact DNA strand. Topo70 residues, whose mutation leads to drug resistance, are highlighted with gray boxes. Mobile phosphodiester of the intact DNA strand is labeled 0P. 36 Burgin et al. 5. 1 Å structure of topotecan bound to the TOP-I–DNA covalent complex solves a 40-year mystery of how the camptothecins bind to their molecular target. The structures explain why the drugs only bind the enzyme-substrate complex and specifically block both DNA relegation and relaxation.
1997 Involvement of amino acids 361 to 364 of human topoisomerase I in camptothecin resistance and enzyme catalysis. Biochem Pharmacol 53:1019–1027. 15. Krogh BO, Shuman S 2000. Catalytic mechanism of DNA topoisomerase IB. Mol Cell 5:1035–1041. 16. Fiorani P, Amatruda JF, Silvestri A, Butler RH, Bjornsti MA, Benedetti P. 1999 Domain interactions affecting human DNA topoisomerase I catalysis and camptothecin sensitivity. Mol Pharm 56:1105–1115. 17. Sheldrick GM. SHELXL-97. University of Göttingen, 1997.
More generally, the experiment also established the feasibility of using electrophilic CPT derivatives to map the orientation of CPT at the interface of the formed protein-nucleic acid binary complex. A conceptually analogous experiment was later described by Pommier et al. (36) involving CPT derivative 20. This compound, which contains an electrophilic chlorine at position 7 of the CPT system, was found to alkylate N-3 of guanosine in the +1 position of the scissile strand of the DNA substrate.
Camptothecins in Cancer Therapy by Val R. Adams
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