Background:

Pepstatin A is a well-known inhibitor of aspartic proteinases with IC50 values of 15 μM, 2 μM,< 5 nM and< 40 nM for human renin, HIV protease, pepsin and cathepsin D, respectively [1, 2].

Pepstatin A is a pentapeptide. It was originally isolated from the microbe. As a most potent renin inhibitor, pepstatinA inhibited porcine renin and human renin at weak acid pH value with IC50 values of 0.32 and 15 μM, respectively. The disadvantage is that, pepstatin Ais hydrophobic. To couple the charged hydrophilic residues to the C-terminal of pepstatinA can increase its solubility. Besides the renin, pepstatin A was also reported to have inhibitory effects on HIV protease and subsequently suppressed the virus replication. In cultured H9 cells, pepstatinA treatment blocked the proteolytic processing of the virus gag precursor and inhibited the production of infectious HIV. Moreover, pepstatin A was found to inhibit osteoclast differentiation due to its inhibitory efficacy of cathepsin D and E [1, 3 and 4].

参考文献:
1. Eid M, Evin G, Castro B, et al.New renin inhibitors homologous with pepstatin.Biochem. J, 1981, 197: 465-471.
2. Sarubbi E, Seneci P F, Angelastro M R, et al. Peptide aldehydes as inhibitors of HIV protease. FEBS letters, 1993, 319(3): 253-256.
3. von der Helm K, Gürtler L, Eberle J, et al. Inhibition of HIV replication in cell culture by the specific aspartic protease inhibitor pepstatin A. FEBS letters, 1989, 247(2): 349-352.
4. Yoshida H, Okamoto K, Iwamoto T, et al. Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation. Journal of biochemistry, 2006, 139(3): 583-590.
>