PMID: 9443934Jan 28, 1998Paper

Recognition of specific sequences in DNA by a topoisomerase I inhibitor derived from the antitumor drug rebeccamycin

Molecular Pharmacology
Christian BaillyM J Waring

Abstract

We investigated the interaction with DNA of two synthetic derivatives of the antitumor antibiotic rebeccamycin: R-3, which is a potent topoisomerase I inhibitor and contains a methoxyglucose moiety appended to the indolocarbazole chromophore, and its aglycone, R-4. Spectroscopic measurements indicate that R-3 intercalates into DNA and that its carbohydrate domain contributes significantly to reinforce the affinity for DNA. Two complementary ligation assays concur that R-3, but not its aglycone counterpart, exerts a significant effect on the curvature and/or the flexibility of DNA. The sugar moiety may be responsible for preferential binding of R-3 to circular (or bent) DNA molecules as opposed to linear DNA fragments. The sequence selectivity of binding to DNA has been studied thoroughly by footprinting with DNase I and two other nucleases. The glycosylated compound is highly selective for nucleotide sequences containing GpT (ApC) and TpG (CpA) steps. The derivative lacking the sugar moiety on the indolocarbazole chromophore binds at essentially identical sites but with considerably lower affinity, so it seems that the chromophore rather than the carbohydrate is responsible for the preferential binding to sequences surrounding ...Continue Reading

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Citations

Nov 23, 2006·Natural Product Reports·César SánchezJosé A Salas
May 18, 2017·Organic & Biomolecular Chemistry·Milena BalazyThomas G Minehan
Mar 20, 2019·Applied Microbiology and Biotechnology·Kathrin PommerehneRainer Krull
Jul 5, 2007·Pediatric Blood & Cancer·Anne-Marie LangevinUNKNOWN Children's Oncology Group
Jan 31, 2015·Organic & Biomolecular Chemistry·Harmanpreet Kaur PanesarThomas G Minehan
Apr 3, 2007·Doklady. Biochemistry and Biophysics·D N KalyuzhnyiO F Borisova
Jun 2, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A W TolcherE K Rowinsky
Feb 24, 2007·The Journal of Antimicrobial Chemotherapy·Bokun ChengYuk-Ching Tse-Dinh
Aug 13, 2009·ChemMedChem·Dmitry N KaluzhnyAlexander A Shtil
Dec 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alejandro D RicartEric K Rowinsky
Jun 22, 2001·Biochimica Et Biophysica Acta·F BarcelóJ Portugal
May 26, 2004·Critical Reviews in Oncology/hematology·Allan Y ChenDavid Gandara

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