Spectroscopic and fluorometric methods were used to study the binding of the anticancer drug @entity5699 to @entity10918 ] and poly[d(G-m5C)] under a variety of solution conditions. Under high-salt conditions that favor the left-handed Z conformation, binding isotherms for the interaction of the drug with poly[d(G-C)] are sigmoidal, indicative of a cooperative binding process. Both the onset and extent of the cooperative binding are strongly dependent upon the ionic strength. The binding data may be explained by a model in which the drug preferentially binds to B-form DNA and acts as an allosteric effector on the B to Z equilibrium. At 2.4 M @entity1219 , binding of as little as one drug molecule per 20 base pairs (bp) results in the conversion of @entity10918 from the Z form entirely to the B form, as inferred from binding data and demonstrated directly by circular dichroism measurements. Similar results are obtained for poly[d(G-m5C)] in 50 mM @entity1219 and 1.25 mM @entity8723 . Under these solution conditions, it is possible to demonstrate the Z to B structural transition in poly[d(G-m5C)] as a function of bound drug by the additional methods of sedimentation velocity and susceptibility to DNase I digestion. The transmission of allosteric effects over 20 bp is well beyond the range of the drug's binding site of 3 bp. Since @entity5699 preferentially binds to alternating @entity10043 - @entity7391 sequences, which are the only sequences capable of the B to Z transition, the allosteric effects described here may be of importance toward understanding the mechanism by which the drug inhibits DNA replicative events.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-range allosteric effects on the B to Z equilibrium by XXXX .

@entity10043 :: ('MESH:C030985', 'Chemical') :: ['purine'] @entity5699 :: ('MESH:D003630', 'Chemical') :: ['daunomycin'] @entity1219 :: ('CHEBI:26710', 'Chemical') :: ['NaCl'] @entity8723 :: ('MESH:D015636', 'Chemical') :: ['MgCl2'] @entity10918 :: ('MESH:C019530', 'Chemical') :: ['poly[d(G-C)]', 'poly[d(G-C)'] @entity7391 :: ('MESH:C030986', 'Chemical') :: ['pyrimidine']
@entity5699 :: (MESH:D003630,Chemical) :: ['daunomycin']
