Projects per year
Abstract
Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development. (C) 2010 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 8334-8340 |
Number of pages | 7 |
Journal | Bioorganic & Medicinal Chemistry |
Volume | 18 |
Issue number | 23 |
DOIs | |
Publication status | Published - 1 Dec 2010 |
Keywords
- Chitinase
- Aspergillus fumigatus
- SCREENING-BASED DISCOVERY
- SACCHAROMYCES-CEREVISIAE
- INVASIVE ASPERGILLOSIS
- CRYSTAL-STRUCTURES
- PROTEIN
- GROWTH
- ALLOSAMIDIN
- HEVAMINE
- COMPLEX
- CELL
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Dive into the research topics of 'Acetazolamide-based fungal chitinase inhibitors'. Together they form a unique fingerprint.Projects
- 2 Finished
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Aref#d: 21559. Molecular Mechanisms of Fungal Cell Wall Assembly (Programme Grant)
van Aalten, D. (Investigator)
1/11/09 → 31/10/14
Project: Research
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Aref#d: 21318. Molecular Mechanisms of O-GlcNAc Signalling (Senior Fellowship Renewal)
van Aalten, D. (Investigator)
1/06/09 → 29/02/16
Project: Research