Type I methionine aminopeptidase from Saccharomyces cerevisiae is a potential target for antifungal drug screening

Ling Ling Chen, Jia Li, Jing Ya Li, Qun Li Luo, Wei Feng Mao, Qiang Shen, Fa Jun Nan, Qi Zhuang Ye

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

AIM: To screen antifungal drug candidates using in vitro and in vivo assays based on type I methionine aminopeptidase from Saccharomyces cerevisiae (ScMetAP1). METHODS: A colorimetric assay suitable for high throughput screening (HTS) using recombinant ScMetAP1 protein expressed in Escherichia coli was established for antifungal lead discovery. A series of pyridine-2-carboxylic acid derivatives were characterized and a chemical library of 12 800 pure organic compounds was screened with the in vitro ScMetAP1 assay. Active compounds from the in vitro assay were further evaluated by a growth inhibition assay on yeast strain with deletion of ScMetAP1 gene mapl in comparison with the wild-type yeast strain and the yeast strain with deletion of type II enzyme (ScMetAP2) gene map2. RESULTS: Active ScMetAP1 inhibitors were identified from HTS. Some of the pyridine-2-carboxylic acid derivatives (compound 2 and 3) had selective inhibition of the growth of map2 deletion yeast and weak inhibition on wild-type yeast growth, while no inhibition on map1 deletion yeast. CONCLUSION: ScMetAP1 is a novel potential target for developing antifungal drugs. The in vitro and in vivo ScMetAP1 assays can serve as tools in discovering antifungal drug candidates.

Original languageEnglish (US)
Pages (from-to)907-914
Number of pages8
JournalActa Pharmacologica Sinica
Volume25
Issue number7
StatePublished - Jul 2004

Keywords

  • Antifungal agent
  • High-throughput screening
  • Methionine aminopeptidase

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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