Peptidyl fluoroketone

HIV protease is an homodimer of C2 symmetry. This enzyme specifically cleaves the precursor polyprotein and affords the proteins required for maturation of the virion and for virus replication. Some pseudosymmetric inhibitors have been conceived on this basis. For example, pseudosymmetric difluoroketones exhibit subnanomolar inhibitions and are active toward infected lymphocyte MT-4 cell lines. Nevertheless, simpler a-peptidyl fluoroketones are also good inhibitors (Figure 7.41). The difluorostanones developed by Merrell-Dow were very efficient toward infected cells. ... 

Zinc metalloproteases can be inhibited by fluoroketones. This inhibition should stem from complexation of the monoanion of the fluoroketone hydrate with zinc. Thus, S-amido and peptidyl fluoroketones inhibit carboxypeptidase and microbial... 

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