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

Representative Nucleotides 5’ 3’ 2

DNA Synthesis by Polymerase DNA template DNA primer 3’-OH dNTPPPi DNA template DNA primer O-N-3’-OH 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.) 3’5’ DNA Pol (repeat) 5’ 3’5’ 3

Novel Template-Competitive DNA Polymerase Inhibitors Doughty & Moore,

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

Template-Competitive RT Inhibitors Doughty, Li, & Lin,

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

GTP Binding Proteins (G-Proteins) 8

Conformational Probes of G-Proteins Seifert & Doughty, unpublished 9

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