SKGQA, a Peptide Derived from the ANA/BTG3 Protein, Cleaves Amyloid-β with Proteolytic Activity
Yusuke Hatakawa,
Rina Nakamura,
Toshifumi Akizawa,
Motomi Konishi,
Akira Matsuda,
Tomoyuki Oe,
Motoaki Saito,
Fumiaki Ito
Affiliations
Yusuke Hatakawa
Department of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Miyagi, Japan
Rina Nakamura
O-Force Co., Ltd., 3454 Irino Kuroshio-cho, Hata-gun 789-1931, Kochi, Japan
Toshifumi Akizawa
O-Force Co., Ltd., 3454 Irino Kuroshio-cho, Hata-gun 789-1931, Kochi, Japan
Motomi Konishi
Department of Integrative Pharmacy, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata 573-0101, Osaka, Japan
Akira Matsuda
Laboratory of Medicinal and Biochemical Analysis, Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshinkai, Kure 737-0112, Hiroshima, Japan
Tomoyuki Oe
Department of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Miyagi, Japan
Motoaki Saito
Department of Pharmacology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku 783-8505, Kochi, Japan
Fumiaki Ito
O-Force Co., Ltd., 3454 Irino Kuroshio-cho, Hata-gun 789-1931, Kochi, Japan
Despite the extensive research conducted on Alzheimer’s disease (AD) over the years, no effective drug for AD treatment has been found. Therefore, the development of new drugs for the treatment of AD is of the utmost importance. We recently reported the proteolytic activities of JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMA), synthetic peptides of nine amino acids each, derived from the Box A region of Tob1 and ANA/BTG3 proteins, respectively. Furthermore, two components of ANA-TA9, ANA-YA4 (YRMI) at the C-terminus end and ANA-SA5 (SKGQA) at the N-terminus end of ANA-TA9, exhibited proteolytic activity against amyloid-β (Aβ) fragment peptides. In this study, we identified the active center of ANA-SA5 using AEBSF, a serine protease inhibitor, and a peptide in which the Ser residue of ANA-SA5 was replaced with Leu. In addition, we demonstrate the proteolytic activity of ANA-SA5 against the soluble form Aβ42 (a-Aβ42) and solid insoluble form s-Aβ42. Furthermore, ANA-SA5 was not cytotoxic to A549 cells. These results indicate that ANA-SA5 is a promising Catalytide and a potential candidate for the development of new peptide drugs targeting Aβ42 for AD treatment.
