DNA-Encoded Chemical Libraries for the Discovery of MMP-3 Inhibitors

• Published in: Bioconjugate chemistry Vol. 19; no. 3; pp. 778 - 785
• Main Authors: Scheuermann, Jörg, Dumelin, Christoph E, Melkko, Samu, Zhang, Yixin, Mannocci, Luca, Jaggi, Madalina, Sobek, Jens, Neri, Dario
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.03.2008
• Subjects: Carbonic Anhydrase II - antagonists & inhibitors; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - pharmacology; Carboxypeptidases A - antagonists & inhibitors; Catalysis; Chemistry; Chromatography, Affinity; Cloning, Molecular; Deoxyribonucleic acid; DNA; DNA - genetics; Drug Design; Enzymes; 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; Tissues; Urokinase-Type Plasminogen Activator - antagonists & inhibitors
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc7004347

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.