DNA-encoded chemical libraries for the discovery of MMP-3 inhibitors.
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.
Scheuermann
Jörg
J
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Strasse10, CH-8093 Zurich, Switzerland.
Dumelin
Christoph E
CE
Melkko
Samu
S
Zhang
Yixin
Y
Mannocci
Luca
L
Jaggi
Madalina
M
Sobek
Jens
J
Neri
Dario
D
D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D043422:Carboxypeptidases A / Q000037:antagonists & inhibitors; D002384:Catalysis; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D015195:Drug Design; D015723:Gene Library; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry / Q000235:genetics*; D061965:Matrix Metalloproteinase Inhibitors; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D002257:Carbonic Anhydrase Inhibitors; D007202:Indicators and Reagents; D061965:Matrix Metalloproteinase Inhibitors; D009841:Oligonucleotides; D011480:Protease Inhibitors; D004247:DNA; D043422:Carboxypeptidases A; D014568:Urokinase-Type Plasminogen Activator; D019278:Matrix Metalloproteinase 3; D024402:Carbonic Anhydrase II