198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

48 J.P. Glusker
d
Fig. 37 d. The chemical formula of a bisintercalator, WP 631 [97]
cin derivative (named WP631, see Fig. 38) is a promising antitumor agent with
a very high affinity for DNA; binding constants are 1.6 ¥ 10 7 M –1 for daunomycin
and 2.7 ¥ 10 11 M –1 for WP631 [98]. Except for some conformational
flexing of the aminosugar, the structures are similar with or without the linker.
The major change is in the region of the linker. It appears that intermolecular
interactions in which a flat aromatic group is intercalated in DNA have some
directionality in that the chromophore in daunomycin and adriamycin complexes
generally lies in the same position even though some of the peripheral
binding interactions are different.
Minor groove binders to DNA are generally A◊ T specific and fit snugly in the
narrow minor groove. Such drugs are replacements for well-ordered water
molecules found in the absence of drugs. Netropsin and distamycin A, which are
pyrrole-amidine oligopeptide antibiotics, bind very tightly to A◊ T regions of