A novel end-to-end binding of two netropsins to the DNA decamers d(CCCCCIIIII)(2), d((CCCBrCCIIIII)-C-5)(2) and d((CBrCCCCIIIII)-C-5)(2)

Netropsin is bound to the DNA decamer d(CCCCClllll)(2), the C-4 bromo deriv ative d(CCCBr(5)CClllll)(2) and the C-2 bromo derivative d(CBr(5)CCCClllll) (2) in a novel 2:1 mode. Complexes of the native decamer and the C-4 bromo derivative are isomorphous, space group P1, unit cell dimensions a = 32.56 Angstrom (32.66), b = 32.59 Angstrom (32.77), c = 37.64 Angstrom (37.71), a = 86.30 degrees (86.01 degrees), beta = 84.50 degrees (84.37 degrees), gam ma = 68.58 degrees (68.90 degrees) with two independent molecules (A and B) in the asymmetric unit (values in parentheses are for the derivative). The C-2 bromo derivative is hexagonal P6(1), unit cell dimensions a = b = 32.1 3 Angstrom, c = 143.92, gamma = 120 degrees with one molecule in the asymme tric unit. The structures were solved by the molecular replacement method. The novelty of the structures is that there are two netropsins bound end-to -end in the minor groove of each B-DNA decamer which has nearly a complete turn. The netropsins are held by hydrogen bonding interactions to the base atoms and by sandwiching van der Waal's interactions from the sugar-phospha te backbones of the double helix similar to every other drug.DNA complex. E ach netropsin molecule spans similar to 5 bp. The netropsins refined with t heir guanidinium heads facing each other at the center, although an orienta tional disorder for the netropsins cannot be excluded. The amidinium ends s tretch out toward the junctions and bind to the adjacent duplexes in the co lumns of stacked symmetry-related complexes. Both cationic ends of netropsi n are bridged by water molecules in one of the independent molecules (molec ule A) of the triclinic structures and also the hexagonal structure to form pseudo-continuous drug decamer helices.