Simple method for studying in vitro protein-protein interactions based on protein complementation and its application in drug screening targeting bacterial transcription

Tsz Fung Tsang, Yangyi Qiu, Lin Lin, Jiqing Ye, Cong Ma, Xiao Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

8 Citations (Scopus)

Abstract

Protein-protein interactions (PPIs) underpin essential cellular processes of all organisms and are increasingly considered as drug targets. A number of techniques have been established to study PPIs; however, development of a simple and cost-effective method for in vitro high throughput screening of PPI inhibitors is still in demand or desirable. We report herein a simple method based on protein complementation for the in vitro study of PPIs, as well as screening of inhibitors against the PPI of interest. We have validated this system utilizing bacterial transcription factors NusB and NusE. Three derivatives of an inhibitor targeting the NusB-NusE interaction were synthesized and characterized with the system, which showed specific inhibition and antimicrobial activities. We have further confirmed the system with the RNA polymeraseâ'σ interaction and an inhibitor. This system is expected to be suitable for more extensive high throughput screening of large chemical libraries. Additionally, our vector system can be easily adapted to study other PPI pairs, followed by inhibitor screening for hit identification in the application of early stage drug discovery.

Original languageEnglish
Pages (from-to)521-527
Number of pages7
JournalACS Infectious Diseases
Volume5
Issue number4
DOIs
Publication statusPublished - 12 Apr 2019

Keywords

  • antimicrobial agent
  • bacterial transcription
  • in vitro drug screening
  • protein complementation assay
  • protein-protein interactions

ASJC Scopus subject areas

  • Infectious Diseases

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