       Document 0875
 DOCN  M9590875
 TI    Design of B-DNA cross-linking and sequence-reading molecules.
 DT    9509
 AU    Walker WL; Kopka ML; Filipowsky ME; Dickerson RE; Goodsell DS; Molecular
       Biology Institute, University of California at Los; Angeles 90095, USA.
 SO    Biopolymers. 1995 May;35(5):543-53. Unique Identifier : AIDSLINE
       MED/95284282
 AB    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.
 DE    Base Sequence  *Cross-Linking Reagents  *Drug Design  DNA/*CHEMISTRY
       Molecular Sequence Data  *Reading Frames  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

