The discovery of shorter synthetic proteolytic peptides derived from Tob1 protein

Abstract We screened nearly 1000 synthetic peptides and found that JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI), which is derived from the BoxA domain in the Tob1 protein, activates both unfolded and folded proMMP-7. Interestingly, the smaller derivative of JAL-AK22, termed JAL-TA9 (YKGSGFRMI) possessed auto-proteolytic activity and cleaved three synthetic peptides fragment (MMP18-33, MMP18-40, and Aβ11-29) under physiological conditions. The k cat of JAL-TA9 was 4.58 × 10 −4  min −1 against MMP18-33 and 6.5 × 10 −4  min −1 against MMP18-40. These kinetic parameters are lower than those of general proteinases like trypsin, for which the k cat is 247.2 × 10 5  min −1 against benzoyl- l -arginine ethyl ester. In addition, a 5-mer peptide derived from JAL-TA9, GSGFR also cleaved Aβ11-29. These proteolytic activities were inhibited by AEBSF (4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride), a serine protease inhibitor. Our results demonstrate that some small synthetic peptides have protease activity. Thus, we propose calling small peptides possessing with protease activity Catalytides ( cataly tic pep tides ). We expect that our findings will stimulate the development of novel Catalytides and related applications such as the development of strategic peptide drugs.