Structure of a DNA-bisdaunomycin complex

Biochemistry
G G HuL D Williams

Abstract

The application of detailed structural data bases has now culminated in the successful design of a new generation of bisanthracyclines that form ultratight DNA complexes [Chaires, J. B., Leng, F., Przewloka, T., Fokt, I., Ling, Y. H., Perez-Soler, R., & Priebe, W. (1997) J. Med. Chem. 40, 261-266]. Daunomycin dimers were designed to bind to DNA in complexes resembling those of monomers intercalated at adjacent sites. The goal of the work described here was to determine, with X-ray crystallography, if a potent member of this newly designed and synthesized class of bisanthracyclines (WP631) binds as intended. WP631 is composed of two daunomycin molecules, linked N3' to N3' by a xylyl group. We have solved the 2.2 A X-ray crystal structure of a complex of WP631 bound to [d(CGATCG)]2. We demonstrate, on a detailed molecular level, that the WP631 design strategy is a success. The structures of WP631 and two daunomycin molecules bound to [d(CGATCG)]2 provide the unprecedented opportunity for detailed comparison of mono- and bis-intercalated complexes of the same chromophore, allowing us to distinguish effects of mono-intercalation from those of bis-intercalation. Differences are focused primarily in the centers of the complexes. DNA ...Continue Reading

References

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Citations

Aug 10, 2000·Journal of Molecular Recognition : JMR·I Haq, J Ladbury
May 9, 2009·Journal of Molecular Modeling·Kendall G BylerWilliam N Setzer
Apr 19, 2002·Biochemical Pharmacology·Silvia VillamarínJosé Portugal
Nov 27, 1999·Pharmacology & Therapeutics·X L Yang, A H Wang
Jul 17, 1998·Current Opinion in Structural Biology·J B Chaires
Mar 4, 2000·Bioorganic & Medicinal Chemistry Letters·A K KarT J Wandless
Dec 22, 2005·Journal of Medicinal Chemistry·José PortugalJonathan B Chaires
Mar 11, 1998·Natural Product Reports·S Neidle, C M Nunn
Feb 15, 2002·Journal of Biomolecular Structure & Dynamics·Sylvia Mansilla, José Portugal
Feb 11, 2004·Journal of Biomolecular Structure & Dynamics·Michael TriebKlaus R Liedl
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Jun 25, 2008·Annual Review of Biophysics·Jonathan B Chaires
Mar 15, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Mhd Ali NazifWilliam S Sheldrick
Aug 20, 2004·European Journal of Biochemistry·Keith R FoxWaldemar Priebe
Apr 30, 2003·Biopolymers·Shelley B HowertonLoren Dean Williams
Jun 11, 2005·Archives of Biochemistry and Biophysics·Monica JainGirjesh Govil
May 7, 2003·Chemico-biological Interactions·Hayet Tayeb-Bel HajArlette Garnier-Suillerot
Sep 7, 2016·Chembiochem : a European Journal of Chemical Biology·Y V SuseelaT Govindaraju
Dec 5, 2008·Journal of Medicinal Chemistry·L Marcus WilhelmssonJan Bergman

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