Summary
Osteoporosis---OP is a systemic disease of bone. It is very common among the old. According to the years of researches, scientists found that in order to prevent this disease, resorption is a core point, which can be achieved by cathepsin L inhibitor.
Researching background
In 1979, Lenaers-Clays found that there is no connection between resorption and the secretion of collagenase. However, the lysosomal cysteine protease, which is cathepsin B, N, L, S, plays a key role in resorption.
Researching progress
Through some researching material and results, it is progressing for scientists to develop new drugs to treat OP with the specific inhibitor of cathepsin L, especially small molecule synthesis inhibitors, such as peptidyl epoxide, peptidyl diazomethane, peptidyl aldehyde and peptidyl monofluoromethanes and so on.
Active site of peptidyl epoxide is epoxy, which can inhibit lysosomal cysteine protease irreversibly. There are E-64, and its similar substances---cathestatin A and B. The former has no specificity ability for lysosomal cysteine protease and disappears so quickly in the body. The last two can be uses to inhibit the calcium release of chick fetus.
Peptidyl diazomethane is mainly depending on the mercapto alkylation of lysosomal cysteine to inhibit lysosomal cysteine protease irreversibly. According to researches, Phe residue can inhibit cathepsin A and B effectively. That reveals that the Phe is necessary for Z-X2-X1-CHN2 to inhibit cathepsin L. However, Z-Phe-Phe-CHN2 can only inhibit cathepsin L, when X1 is large hydrophobic residue.
Peptidyl aldehyde is a kind of reversible inhibitor, which react with mercapto of the lysosomal cysteine protease to form hemiketal thioaldehyde. Leu-peptin and Antipain are the earlest peptidyl aldehyde with the ability of anti-OP activity. However, the main disadvantage of peptudyl aldehyde is poor selectivity, and it cannot only inhibit the lysosomal cysteine protease, but also some serine proteases.
In a word, the function of cathepsin L inhibitor to OP is still under research. And experiments in vivo and vitro show great possibility for cathepsin L inhibitor to develop new drugs for OP.