用生物筛选识别药物分子伴侣和构象抑制剂和传染病

Title:Biophysical Screening for Identifying Pharmacological Chaperones and Inhibitors Against Conformational and Infectious Diseases

Volume: 17 Issue: 13

Author(s): Adrián Velazquez-Campoy, Javier Sancho, Olga Abian, Sonia Vega

Affiliation:

关键词: 变构和竞争性抑制剂构象病，实验分子筛选，荧光热转移，传染病，配体诱导的稳定，药物分子伴侣蛋白的稳定性。

摘要: Experimental and computational screenings are currently widespread tools for identifying either potential ligands for a given target or potential targets for a given chemical compound. In particular, ligand-induced stabilization against thermal denaturation (or thermal shift assay) is an easy and convenient experimental procedure for finding compounds able to control the activity of a protein target (e.g., allosteric or competitive inhibitors interfering with its activity, allosteric activators enhancing its activity, or pharmacological chaperones avoiding aggregation, unfolding or degradation). Despite its simplicity the thermal shift assay does not lack some important drawbacks. Here we describe this methodology, its application to structured and unstructured protein targets, and we discuss successful cases of identification of bioactive compounds for conformational disorders associated to loss of function (phenylketonuria) and infectious diseases (gastric ulcer and hepatitis C).

Cite this article as:

Adrián Velazquez-Campoy, Javier Sancho, Olga Abian, Sonia Vega , Biophysical Screening for Identifying Pharmacological Chaperones and Inhibitors Against Conformational and Infectious Diseases, Current Drug Targets 2016; 17 (13) . https://dx.doi.org/10.2174/1389450117666160201110449