Towards Functional Metal-Mediated DNA Base-Pairs

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Christopher Switzer at the University of California-Riverside, to develop metal mediated base pairs that are capable of participating in information transfer reactions alongside their natural counterparts. To accomplish this objective, metal mediated base pair motifs will be developed with optimal shape and size for acceptance by natural enzymes. The work under the award will build on preliminary studies by the PI's laboratory to create a next generation metal mediated base pair capable of such function. This next generation base pair uses a tridentate purine-like component and a monodentate pyrimidine-like component to coordinate a divalent metal ion, such as Cu2+. The function of metal mediated base pairs with natural polymerase enzymes will be explored and optimized by employing a range of different monodentate nucleotides chosen on the basis of synthetic expediency and known optimal design features.Watson-Crick base pairs encode genetic information in all organisms. While natural base pairs rely on hydrogen bonds for recognition, other weak or reversible interactions hold promise for the creation of non-standard base pairs. Metal-mediated bonds have been shown recently to replace hydrogen bonds between non-standard bases in the DNA helix. The next steps in the progression to achieve functional metal-mediated base pairs are therefore now within reach. The program of study will provide a solid training ground for graduate students in chemical biology. Additionally, research opportunities for undergraduate students will be offered during the proposal period, including a summer undergraduate research position for underrepresented minorities or women.