Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for FAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-d-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets.

Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.

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The anti-fatigue activity evaluation was carried out with black soybean peptide in mice. The results show that, the middle and high dose active peptides can significantly （P＜0.01） prolong swimming time, blood lactic acid can be reduced notable （P＜0.01）, and improving the liver glycogen storage status greatly （P＜0.01） by infusing with black soybean peptide. The results suggest that black soybean peptide has obvious anti-fatigue effect, and the anti-fatigue action will improve by increasing dose.

Black soybean peptides (BSPs) with potent antioxidant activity were purified from black soybean protein hydrolysates (BSH) by using the ultrafiltration (UF) and macroporous adsorption resin (MAR), andin vivoantioxidant activity of the fraction BSP-DA-c was evaluated in aging mice induced byD-galactose. The results showed that orally administration of BSP-DA-c fraction at the dose of 500 and 1000 mg/kg per day could remarkably increase (P<0.05) the activity of SOD and GSH-Px in liver and the activity of GSH-Px in serum, the contents of MDA in serum and liver were reduced significantly (P<0.05), inferred that BSP-DA-c had strong antioxidant activity in mice.