Optimizing the binding of fullerene inhibitors of the HIV-1 protease through predicted increases in hydrophobic desolvation.

摘要: We have developed and applied a computational strategy to increase the affinity of fullerene-based inhibitors HIV protease. The result is ∼50-fold in from previously tested fullerene compounds. based on design derivatives which may potentially hydrophobic desolvation upon complex formation, followed by docking hypothetical into protease active site assessment model complexes so formed. are generated program DOCK then analyzed for desolvated surface. amount surface was compared with compound, if this significantly greater, it selected as target. Using approach, two targets were identified synthesized, using different synthetic approaches:  diphenyl C60 alcohol (5) cyclopropyl derivative Bingel (Chem. Ber. 1993, 126, 1957−1959) diisopropyl cyclohexyl alcohol...