CHED 1339 |
| Enzyme inhibitors are often used to develop medications to treat viral and bacterial diseases. Our goal is nucleotide inhibitors which can inhibit viral nucleic acid polymerases as target drug candidates. The results presented here demonstrate the effectiveness of three inhibitors synthesized from 2-thioetheno dAMP: 1) 2-S(2,4-dichlorophenacyl)etheno-dAMP 2) 2-S(4-chlorophenacyl)etheno-dAMP and 3) 2-S-phenacyl-etheno-dAMP. The target compounds were synthesized, purified by ethanol precipitation and chromatography, and then converted to triphosphates or aminoethyl phosphoramides, followed by DEAE and HPLC purification. The effectiveness of the inhibitors is determined in a five component assay system using a tris buffer, pH 8.5. The assays are initiated with enzyme, allowed to react for 30 minutes, and quenched with EDTA. The substrate inhibition is determined as the inhibition of 3H·TTP incorporation into poly(A)·oligo(dT10) substrate, and calculated by non-linear regression as IC50 and KI. The inhibitory efficiency and mechanisms will be presented. |
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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 |