@article{APS8289,
author = {Ling-ling CHEN and Jia LI and Jing-ya LI and Qun-li LUO and Wei-feng MAO and Qiang SHEN and Fa-jun NAN and Qi-zhuang YE},
title = {Type I methionine aminopeptidase from Saccharomyces cerevisiae is a potential target for antifungal drug screening},
journal = {Acta Pharmacologica Sinica},
volume = {25},
number = {7},
year = {2016},
keywords = {},
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 map1 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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/8289}
}