Development of DHQ-based chemical biology probe to profile cellular targets for HBV

Bioorg Med Chem Lett. 2020 Dec 1;30(23):127615. doi: 10.1016/j.bmcl.2020.127615. Epub 2020 Oct 17.

Abstract

Chronic hepatitis B virus (HBV) infection has been a serious public health burden worldwide. Current anti-HBV therapies could not eliminate HBV ultimately. Considering the characteristics of HBV, it is impossible to be entirely cured based on current therapies. Therefore, it is urgently needed to develop novel therapeutic agents with new mechanism of action. The dihydroquinolizinone (DHQ) derivatives exhibited potent anti-HBV activity by decreasing HBV DNA and HBsAg level in an obscure mechanism of action. In this study, we have optimized the DHQ scaffold, developed the photoaffinity probe, with which to identify potential binding proteins.

Keywords: Activity-based proteome profiling (ABPP); Dihydroquinolizinone (DHQ); Hepatitis B virus (HBV); Photoaffinity labeling; RNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacology*
  • Chromatography, Liquid
  • Click Chemistry
  • Hepatitis B virus / drug effects*
  • Molecular Structure
  • Photoaffinity Labels / chemical synthesis
  • Photoaffinity Labels / pharmacology*
  • Proteome / analysis
  • Proteome / chemistry
  • Proteomics
  • Quinolizines / chemical synthesis
  • Quinolizines / pharmacology*
  • Structure-Activity Relationship
  • Tandem Mass Spectrometry
  • Viral Proteins / analysis*
  • Viral Proteins / chemistry

Substances

  • Antiviral Agents
  • Photoaffinity Labels
  • Proteome
  • Quinolizines
  • Viral Proteins