Topologically constrained DNA intercalators: Synthesis and DNA binding studies
The synthesis and DNA binding properties of three macrocyclic diacridines (31, 32 and 33) is discussed. The two acridines are connected by linker chains at the 4- and 9-positions. Macrocycles 31 and 32 are linked via spermine at the 9-position and have been shown to bind to DNA by bisintercalation using absorption spectroscopy titrations, thermal denaturation studies, and viscometric titrations of both calf thymus DNA and closed circular supercoiled DNA. Macrocycle 31 dissociates 10 to 40 times slower from poly(d(A-T)) $\sb2$ and poly(d(G-C)) $\sb2$ than its analogous mono-linked analogue, spermine diacridine (7). $\sp1$H NMR studies of 31 complexed to d(CGCG)$\sb2$ indicate that the macrocycle binds to DNA by formation of a catenated complex in which one linking chain is located in opposite grooves of the DNA. The NMR studies and absorption spectral titrations suggest that 31 binds by insertion of the acridines on each side of one base pair in violation of the neighbor exclusion principle.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign