Comparison of the catalytic activities of 5-mer synthetic peptides derived from Box A region of Tob/BTG family proteins against the amyloid-beta fragment peptides

Abstract

We previously reported the catalytic activity of 9-mer peptide, JAL-TA9 (YKGSGFRMI), derived from the Box A region of Tob/BTG family of proteins. This was the first report of the catalytic activity of shorter synthetic peptides. Therefore, we used ‘Catalytide’ (catalytic peptide) as the general term for peptides possessing the hydrolase activity. NMR study of JAL-TA9 suggested that the minimum sequence required for the catalytic activity is a 5-mer peptide (GSGFR). In this study, we examined the catalytic activity of this 5-mer peptide against Aβ fragment peptides, Aβ1-20 and Aβ11-29, to find the next Catalytide. Activity of all peptides identified as Catalytides, especially, GQAYR (BTG3) and GQAFR (BTG4), was higher activity than that of GSGFR (Tob1 and 2) and GSGYR (BTG1 and 2). The cleavage mechanism of these Catalytides is still not well understood and needs further investigation. Nonetheless, 5-mer Catalytides are attractive candidates for the development of peptide drugs as a new strategy for treating Alzheimer’s disease (AD). Abbreviations: APP: Amyloid Precursor Protein; Aβ: Amyloid Beta; AD: Alzheimer’s Disease; HSA: Human Serum Albumin; TFA: Trifluoroacetic Acid; HPLC: High-Performance Liquid Chromatography; NMR: Nuclear Magnetic Resonance.