| Autor: |
Akihiro Ishiwata, Satoru Narita, Kenta Kimura, Katsunori Tanaka, Kiyotaka Fujita, Shinya Fushinobu, Yukishige Ito |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Bioorganic & Medicinal Chemistry. 75:117054 |
| ISSN: |
0968-0896 |
| DOI: |
10.1016/j.bmc.2022.117054 |
| Popis: |
To understand the precise mechanism of the glycoside hydrolase (GH) family 127, a cysteine β-l-arabinofuranosidase (Arafase) - HypBA1 - has been isolated from Bifidobacterium longum in the human Gut microbiota, and the design and synthesis of the mechanism-based inhibitors such as l-Araf-haloacetamides have been carried out. The α-l-Araf-azide derivative was used as the monoglycosylamine equivalent to afford the l-Araf-chloroacetamides (α/β-1-Cl) as well as bromoacetamides (α/β-1-Br) in highly stereoselective manner through Staudinger reaction followed by amide formation with/without anomerization. Against HypBA1, the probes 1, especially in the case of α/β-1-Br inhibited the hydrolysis. Conformational implications of these observations are discussed in this manuscript. Additional examinations using l-Araf-azides (α/β-5) resulted in further mechanistic observations of the GH127/146 cysteine glycosidases, including the hydrolysis of β-5 as the substrate and oxidative inhibition by α-5 using the GH127 homologue. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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