Inhibition of HIV-1 protease

There are, indeed, many biological implications that have been triggered by the advent of fullerenes. They range from potential inhibition of HIV-1 protease, synthesis of dmgs for photodynamic therapy and free radical scavenging (antioxidants), to participation in photo-induced DNA scission processes [156, 157, 158, 159, 160, 161, 162 and 163]. These examples unequivocally demonstrate the particular importance of water-soluble fullerenes and are summarized in a few excellent reviews [141, 1751. 

Friedman S H, DeCamp D L, Si]besma R, Srdanov G and WudI F 1993 Inhibition of HIV-1 protease by fullerene derivatives model building studies and experimental verifioation J. Am. Chem. See. 115 6506-9... 

Kaldor SW, Appelt K, Fritz JE, Hammond M, Crowell , Baxter AJ, Hatch SD, Wiskerchen MA, Muesing MA. A systemic study of P1-P3 spanning si dechains for the inhibition of HIV-1 protease. Bioorg. Med. Chem. Lett. 1995 5 715-720. 

Tummino PJ, Ferguson D, Hupe L, Hupe D. Competitive inhibition of HIV-1 protease by 4-hydroxy-benzopyran-2-ones and 4-hydroxyphenylpyran-2-ones. Biochem. Biophys. REs. Commun. 1994 200 1658-1664. 

FIGURE 7.14. Schematic illustration of the inhibition of HIV-1 protease homodimer by amphiphiles that tether two peptides mimicking the interface of the protease. Optimization of the potency of the inhibitor is achieved by varying the residues on the amphiphiles, as shown below die illustration. 

Bowman MJ, Byrne S, Chmielewski J (2005) Switching between allosteric and dimerization inhibition of HIV-1 protease. Chem Biol 12 439 144... 

The judicious introduction of a fluorine atom into the HIV-1 protease inhibitor indinavir (33) and epi-indinavir (34) provided an opportunity to assess the effect of F-OH interactions on biological properties related to conformational disposition [71], The four fluorinated derivatives 35-38 were prepared with the anticipation of complex effects due to the F atom which was expected to affect the acidity of the OH and influence the population of conformers in addition to affecting steric interactions and solvation. The Kj data for the inhibition of HIV-1 protease are summarized in Table 2 and reveal interesting profiles. 

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