Bibliographic Details
| Title: |
Mechanism-Based Allylic Carbasugar Chlorides That Form Covalent Intermediates with α- and β-Galactosidases |
| Authors: |
Oluwafemi Akintola, Sandeep Bhosale, Andrew J. Bennet |
| Source: |
Molecules, Vol 29, Iss 20, p 4870 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Organic chemistry |
| Subject Terms: |
mechanism-based, glycoside hydrolase, covalent inhibitor, carbasugar, selectivity, galactosidase, Organic chemistry, QD241-441 |
| More Details: |
Glycoside hydrolases have been implicated in a wide range of human conditions including lysosomal storage diseases. Consequently, many researchers have directed their efforts towards identifying new classes of glycoside hydrolase inhibitors, both synthetic and from natural sources. A large percentage of such inhibitors are reversible competitive inhibitors that bind in the active site often due to them possessing structural features, often a protonatable basic nitrogen atom, that mimic the enzymatic transition state. We report that mechanism-based small molecule galacto-like configured cyclohexenyl carbasugars form reversible covalent complexes with both α-galactosidase and β-galactosidase. In addition, we show that the β-galactosidase from Aspergillus oryzae reacts with three different carbasugar inhibitors, with three different second-order rate constants (kinact/Ki), to give the same enzyme–carbasugar covalent intermediate. The surprising observation that the α-galacto-configured inhibitor covalently labels the A. oryzae β-galactosidase highlights the catalytic versatility of glycoside hydrolases. We expect that cyclohexenyl covalent inhibitors will become an important class of compounds in the chemical biologist’s tool box. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/29/20/4870; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules29204870 |
| Access URL: |
https://doaj.org/article/b22d705092f045858673c53a8b27fbd2 |
| Accession Number: |
edsdoj.b22d705092f045858673c53a8b27fbd2 |
| Database: |
Directory of Open Access Journals |
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