9506300 Williams A molecular understanding of DNA-porphyrin interactions will facilitate design of a host of technologically useful molecules such as new artificial nucleases, structural probes and conjugates, photodynamic agents, biomaterials and nano-devices. Porphyrins interact with DNA by several modes. Porphyrins intercalate, groove bind, and may bind in novel, currently uncharacterized modes. Some porphyrins form non-covalent complexes with DNA while others are reactive, causing strand scission, base release and other reactions. One attractive aspect of porphyrins is the systematic manner in which DNA mode of binding and reactivity vary with porphyrin shape, metal center, charge and additional structural and physical properties. These parameters are easily manipulated because techniques for elaboration of porphyrin structure are extensively developed. However, no detailed 3-D structures of DNA- porphyrin complexes have been determined thus far. The goal of this proposal is to determine 3-dimensional x-ray structures of DNA-porphyrin complexes. Initial work will focus on previously obtained crystals of the following DNA-porphyrin complexes: (1) (Cu)TMPyP4 - CGATCG, (2) (Cu)TMPyP4 - CGATICG, (3) (Cu)TMPyP4 - CGATCG - K2PtCI, (4) (Cu)TMPyP4 - CGATCG - SmCI3, (5) (Cu)TMPyP4 - ICGATCG, (6) (Ni)TMPyP4 - CGATCG, (7) (Pd)TMPyP4 - CGATCG, (8) (Cu)TMPyP4 - CGCG, where IC= 5-iodoC and TMPyP4 = meso-(4-(N- tetra-methylpyridyl))porphyrin . X-ray intensity data has been obtained from several of these crystals and structure solution is in progress. Teaching Philosophy. Georgia Tech is a combined research and teaching institution. Training pof undergraduates, graduate students and post-doctoral associates is an essential part of the PI's research program. The PI's goals are to teach and conduct research in an academic environment. Motivation for classroom teaching is enjoyment, intellectual challenge, and to gain and maintain breadth of knowledge that research alone does not necessarily foster. The PI has developed new curricula for several courses. His teaching philosophy is to excite students by incorporating the latest techniques and results into the curriculum. %%% Porphyrins and porphyrin-like molecules are brightly colored, biologically critical molecules that give color to hemoglobin and chlorophyll. Porphyrins can interact by several modes with DNA, the genetic material. A molecular understanding of DNA-porphyrin interactions will facilitate design of a host of technologically useful molecules such as new artificial nucleases, structural probes and conjugates, biomaterials and nano-devices. Porphyrins sometimes intercalate, sliding between base pairs and increasing the length of DNA. Under other conditions porphyrins bind in the DNA grooves. In some instances porphyrins may bind to DNA by novel, uncharacterized modes. Certain porphyrins are reactive, causing DNA strand scission, base release and other reactions. DNA mode of binding and reactivity vary with porphyrin shape, metal center, charge and additional structural and physical properties. These parameters are easily manipulated. However, thus far no detailed 3-D structures of DNA-porphyrin complexes have been determined. X-ray crystallography is a method by which molecules can be visualized in atomic detail. For this work, x-ray crystallography will be used to visualize complexes of DNA with porphyrins. Crystals of DNA-porphyrin complexes will be grown and a beam of x-rays will be directed through each crystal. The atoms of the crystal scatter the x-rays. After collection and proper processing of the intensities of scattered x-rays, the positions of the atoms of the DNA and of the bound porphyrin molecule can be reconstructed. ***
