Application of Computational Chemistry in Protein Binding Assays: Synthesis and Evaluation of New anti HIV drugs

QUEVEDO, M.A.

Golden School of Mines, Golden, Colorado, Estados Unidos de América.

Taller; 6th Annual Summer School in Green Chemistry and Sustainability; 2008

American Chemical Societu

The binding to plasmatic proteins has been identifyed as a key pharmacokinetic property for the design of safer anti HIV drugs. Zidovudine (AZT, Fig. 1) was the first anti HIV drug approved by the FDA, and although its clinical efficacy has longly been demonstrated, important toxicity issues are still associated with its use.In order to obtain new anti HIV drugs with less toxic effects, we have designed new prodrugs of AZT with higher affinity than AZT to plasmatic proteins , and mainly targeting Human Serum Albumin (HSA), the most abundant protein in plasma.Our research activities are organized basically in four stages (Fig.2), presenting in this work the methodologies applyed to predict the binding to HSA of two new derivatives of AZT, establishing a correlation between experimental data and energetic components calculated.