Nucleotide Chemistry and Biochemistry at SLU

1. 1 Nucleotide Chemistry and Biochemistry at SLU Michael B. Doughty Associate Professor of Biochemistry Department of Chem & Phys Southeastern Louisiana University

2. 2 Representative Nucleotides 5’ 3’

3. 3 DNA Synthesis by Polymerase DNA Pol DNA template DNA template 3’ 5’ 3’ 5’ 3’-OH 5’ 5’ O-N-3’-OH DNA primer dNTP PPi DNA primer (repeat) Inhibitors of DNA polymerase are traditionally used as anti-metabolites to treat cancer and DNA virus infections (e.g., Herpes simplex I and II; Cytomegalovirus; Hepatitis B virus, etc.)

4. 4 Novel Template-Competitive DNA Polymerase Inhibitors Doughty & Moore, 1996

5. 5 DNA Synthesis by Reverse Transcriptase Reverse transcriptase (RT) is a retroviral enzyme required for incorporation of a viral RNA genome into host DNA RT RT RNA RNA DNA Integration and viral particle production RT DNA DNA DNA RT inhibitors are or could be used to treat retroviral disease (HIV; Hepatitis A and C; Rabies virus; Mumps and Influenza viruses)

6. 6 Template-Competitive RT Inhibitors Doughty, Li, & Lin, 2001

7. 7 Structural Comparison of RT and DNA Pol Inhibitors DNA Pol TC inhibitors RT inhibitors Conformationally, the etheno group forces a population where the side chain is bent under the sugar

8. 8 GTP Binding Proteins (G-Proteins)

9. 9 Conformational Probes of G-Proteins Seifert & Doughty, unpublished

10. 10 Techniques 1. Chemical synthesis of nucleotides. 2. Conformational analysis of nucleotides and enzyme/protein binding sites. 3. Kinetic analysis and other bioassays.