Design of B-DNA cross-linking and sequence-reading molecules

W L WalkerD S Goodsell


We report the design of hybrid molecules to bind in the minor groove of B-DNA, which combine DNA alkylating and cross-linking ability for increased chemotherapeutic efficacy, with sequence specificity, to minimize side effects. Optimal linkage geometries have been determined for the synthesis of bis-anthramycin and anthramycin-netropsin hybrid molecules. Earlier studies on linked drugs have typically been based on molecular mechanics calculations. This work, in contrast, uses the observed crystal structures of a netropsin/DNA complex and a new anthramycin/DNA complex to determine the exact spacing between two individual drugs when bound in the minor groove of B-DNA. Molecular linkers then are designed and tested between these two experimental positions, to form a chimeric or bis-linked compound molecule. A linked anthramycin-netropsin molecule has been designed specifically to target the polypurine tract second-strand primer site of the reverse transcriptase of HIV-1.


Jul 24, 1992·Journal of Medicinal Chemistry·W Wang, J W Lown
Aug 7, 1992·Journal of Medicinal Chemistry·J J WangL H Hurley
Mar 7, 1991·Nucleic Acids Research·J D FarmerJ W Suggs
Jan 1, 1991·Archives of Virology·O HungnesB Grinde
Jan 1, 1990·Proteins·D S Goodsell, A J Olson
Dec 26, 1989·Biochemistry·T R KrughM P Stone
Jun 25, 1985·Journal of Molecular Biology·M L KopkaR E Dickerson
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R E DickersonS Neidle
May 13, 1983·Science·S KirkpatrickM P Vecchi

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Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·D E Wemmer
Jun 27, 1997·Journal of Molecular Biology·G W HanR E Dickerson
Feb 19, 2002·Chemical Reviews·Scott R. Rajski, Robert M. Williams
Sep 20, 2002·Journal of Medicinal Chemistry·Kamesh RastogiTsann-Long Su

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