En förstudie för framtagning av HIV-proteashämmare : Me-too läkemedel till indinavir

Sammanfattning:

The purpose of this report was to develop theoretical analogues of indinavir that ispredicted to bind well to HIV-I protease, wild type and mutants. These analogues aremeant for experimental testing by enzyme assay and cell-based β-galactosidase activityassay to see if they have potential to be new protease inhibitors for HIV. 80 analoguesprovided by the company Syntesdesign AB were analyzed with the software Glide.This was done to find out the binding affinities to HIV-I protease and some of its mostcommon mutations. The results were analyzed to see how different structuralelements contributed to high affinity. 48 new analogues were suggested and alsoanalyzed based on the results of the computer simulations. The 30 analogues with thepredicted highest affinity to the wild type protease and the mutations were selectedand ranked. All but one of these analogues were predicted to have better binding tothe protease than Indinavir.