DNA-encoded chemical libraries for the discovery of MMP-3 inhibitors

Bioconjug Chem. 2008 Mar;19(3):778-85. doi: 10.1021/bc7004347. Epub 2008 Feb 7.

Abstract

Encoded self-assembling chemical (ESAC) libraries are characterized by the covalent display of chemical moieties at the extremity of self-assembling oligonucleotides carrying a unique DNA sequence for the identification of the corresponding chemical moiety. We have used ESAC library technology in a two-step selection procedure for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, yielding novel inhibitors with micromolar potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carboxypeptidases A / antagonists & inhibitors
  • Catalysis
  • Chromatography, Affinity
  • Cloning, Molecular
  • DNA / genetics*
  • Drug Design
  • Gene Library
  • Humans
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Matrix Metalloproteinase 3 / chemistry
  • Matrix Metalloproteinase 3 / genetics*
  • Matrix Metalloproteinase Inhibitors*
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Electrospray Ionization
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors

Substances

  • Carbonic Anhydrase Inhibitors
  • Indicators and Reagents
  • Matrix Metalloproteinase Inhibitors
  • Oligonucleotides
  • Protease Inhibitors
  • DNA
  • Carboxypeptidases A
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 3
  • Carbonic Anhydrase II