Screening-based discovery of Aspergillus fumigatus plant-type chitinase inhibitors.
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ABSTRACT:
SUBMITTER: Lockhart DE
PROVIDER: S-EPMC4158421 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
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Screening-based discovery of Aspergillus fumigatus plant-type chitinase inhibitors.
Lockhart Deborah E A DE Schuettelkopf Alexander A Blair David E DE van Aalten Daan M F DM
FEBS letters 20140722 17
A limited therapeutic arsenal against increasing clinical disease due to Aspergillus spp. necessitates urgent characterisation of new antifungal targets. Here we describe the discovery of novel, low micromolar chemical inhibitors of Aspergillus fumigatus family 18 plant-type chitinase A1 (AfChiA1) by high-throughput screening (HTS). Analysis of the binding mode by X-ray crystallography confirmed competitive inhibition and kinetic studies revealed two compounds with selectivity towards fungal pla ...[more]
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