V. Janout et al., EVIDENCE FOR HIGHLY COOPERATIVE BINDING BETWEEN MOLECULAR UMBRELLA-SPERMINE CONJUGATES AND DNA, Bioconjugate chemistry, 8(6), 1997, pp. 891-895
Double- and tetrawalled molecular umbrella-spermine conjugates (I and
II) have been synthesized, and their binding to calf thymus DNA (CT-DN
A), poly[d(AT)], and poly[d(GC)] compared with that of a single-walled
analogue (III). At moderate salt concentrations (8 mM NaCl), I and II
show significantly greater affinity toward each DNA, relative to III;
at high salt concentrations (150 mM NaCl), strong binding of I and II
(but not III) was maintained toward poly[d(GC)]. Examination of the i
nfluence of I-III on the melting behavior of poly[d(AT)] has provided
strong evidence that the binding of I and II reflects highly cooperati
ve interactions among DNA-bound conjugates and that the DNA duplex ser
ves as a nucleation site for umbrella aggregation. The implications of
these findings for the rational design of novel drug conjugates that
operate at the nuclear level, and also novel transfection agents, are
briefly discussed.