Unbiased binding assays for discovering small-molecule probes and drugs

Bioorg Med Chem. 2012 Mar 15;20(6):1979-89. doi: 10.1016/j.bmc.2011.11.071. Epub 2011 Dec 24.

Abstract

2011 marks the 10-year anniversary of milestone manuscripts describing drafts of the human genome sequence. Over the past decade, a number of new proteins have been linked to disease-many of which fall into classes that have been historically considered challenging from the perspective of drug discovery. Several of these newly associated proteins lack structural information or strong annotation with regard to function, making development of conventional in vitro functional assays difficult. A recent resurgence in the popularity of simple small molecule binding assays has led to new approaches that do not require knowledge of protein structure or function in advance. Here we briefly review selected methods for executing binding assays that have been used successfully to discover small-molecule probes or drug candidates.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery*
  • Humans
  • Mass Spectrometry / methods
  • Models, Molecular
  • Protein Binding
  • Proteins / chemistry
  • Proteins / metabolism*
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Surface Plasmon Resonance / methods

Substances

  • Proteins
  • Small Molecule Libraries