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Peptides. 2019 Jun;116:71-77. doi: 10.1016/j.peptides.2019.03.005. Epub 2019 Mar 28.

The discovery of shorter synthetic proteolytic peptides derived from Tob1 protein.

Author information

1
O-Force Co. Ltd., 3454 Irino, Kuroshio-cho, Hata-gun, Kochi, 789-1931, Japan; Department of Pharmacology, Kochi Medical School, Kochi University, Kohasu Oko-cho, Nankoku, Kochi, 783-8505, Japan; Laboratory of Clinical Analytical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan.
2
Laboratory of Clinical Analytical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan. Electronic address: momizit0510@gmail.com.
3
Laboratory of Clinical Analytical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan.

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 kcat 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 kcat is 247.2 × 105 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 (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications such as the development of strategic peptide drugs.

KEYWORDS:

Catalytide; Serine protease-like peptide; Tob1

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