Evaluation of superior BACE1 cleavage sequences containing unnatural amino acids

Taeko Kakizawa; Akira Sanjoh; Akane Kobayashi; Yasunao Hattori; Kenta Teruya; Kenichi Akaji

doi:10.1016/j.bmc.2011.03.056

Evaluation of superior BACE1 cleavage sequences containing unnatural amino acids

Taeko Kakizawa, Akira Sanjoh, Akane Kobayashi, Yasunao Hattori, Kenta Teruya, Kenichi Akaji

Research output: Contribution to journal › Article

4 Citations (Scopus)

Abstract

A recombinant form of BACE1 (β-site amyloid precursor protein cleaving enzyme-1) corresponding to positions 46-454 of the extracellular domain of the original membrane enzyme was prepared. The recombinant BACE1 (rBACE1) had the kinetic parameters K_m = 5.5 μM and k_cat = 1719 s ^-1. Using several libraries of substrates containing unnatural amino acids, the specificity of rBACE1 was evaluated. LC/MS of digests derived from the libraries clarified that a dodecapeptide containing unnatural amino acids at P₂ to P1^′ was a superior cleavage sequence.

Original language	English
Pages (from-to)	2785-2789
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	9
DOIs	https://doi.org/10.1016/j.bmc.2011.03.056
Publication status	Published - 2011 May 1
Externally published	Yes

Keywords

Amyloid peptide
BACE1
Substrate specificity
Unnatural amino acid

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Kakizawa, T., Sanjoh, A., Kobayashi, A., Hattori, Y., Teruya, K., & Akaji, K. (2011). Evaluation of superior BACE1 cleavage sequences containing unnatural amino acids. Bioorganic and Medicinal Chemistry, 19(9), 2785-2789. https://doi.org/10.1016/j.bmc.2011.03.056

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AU - Akaji, Kenichi

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