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 Km = 5.5 μM and kcat = 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 |
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Pages (from-to) | 2785-2789 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 19 |
Issue number | 9 |
DOIs | |
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