Design and synthesis of template competitive reverse transcriptase inhibitors

CHED 1332

Tao Lin, Tao.Lin@selu.edu, Department of Chemistry & Physics, Southeastern, SLU Box 10878, Hammond, LA 70402-0878 and Michael B. Doughty, mdoughty@selu.edu, Department of Chemistry, Southeastern Louisiana University, SLU 10878, Hammond, LA 70402.
Many viral diseases threaten people's health and there are too few vaccines or viral inhibitors to fight against these viruses. One example is the HIV retrovirus. HIV encodes the enzyme reverse transcriptase (RT) that converts single-stranded RNA genome of the retrovirus into double-stranded DNA before the cell begins viral replication. The goal of our research is to produce nucleotide inhibitors that can directly inhibit the activity of RT and prevent viral replication. In general, synthesis of the inhibitors begins with conversion of dAMP into etheno-dAMP. After hydrolysis of etheno-dAMP, a thio group is installed into the 2 position on the ring, forming 2-thioetheno-dAMP. Three inhibitor base molecules derived from this template include: 1) 2-S-(3,4-dichlorobenzyl)-etheno-dAMP, 2) 2-S-(4-chlorobenzyl)-etheno-dAMP, and 3) 2-S-benzyl-etheno-dAMP. These monophosphates are modified into triphosphates or phosphoramides, followed by chromatography and HPLC purification. The results of enzyme assays performed to test the inhibition of HIV RT will be presented.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007