STRUCTURE OF A DNA-PORPHYRIN COMPLEX Loren Dean Williams, Leigh Ann Lipscomb, Fang Xiao Zhou, Steven R. Presnell, Rebecca J. Woo, Mary E. Peek, School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400

We report the 2.4 Å structure of a complex in which CuTMPyP4 [copper (II) meso-tetra(N-methyl-4-pyridyl)porphyrin] flips a base out of the helical stack of duplex d(CGATCG). The porphyrin system is located within the helical stack, with the copper atom near the helical axis. The porphyrin binds by normal intercalation between the C and G of 5' TCG 3' and by extruding the C of 5' CGA 3'. The DNA hexamer forms a distorted right-handed helix with only four normal cross-strand Watson-Crick base pairs. Two pyridyl rings of the porphyrin are located in each groove of the DNA. The complex appears to be extensively stabilized by electrostatic interactions between positively-charged nitrogen atoms of the pyridyl rings and negatively-charged phosphate oxygen atoms of the DNA. Favorable electrostatic interactions appear to draw the porphyrin into the duplex interior. These favorable interactions offset unfavorable steric clashes between the pyridyl rings and the DNA backbone. We believe these pyridyl-backbone clashes extend the DNA along its axis and preclude formation of van der Waals stacking contacts in the interior of the complex. The unusual lack of van der Waals stacking contacts observed in the porphyrin complex destabilizes the DNA duplex and decreases the energetic cost of local melting. Thus extrusion of a base appears to be facilitated by pyridyl-DNA steric clashes.

This work was supported in part by the American Cancer Society (NP-912).