Discovering non-peptidic inhibitors for matrix metalloproteinases with their recombinant catalytic domains

Qizhuang Ye, Linda Johnson, Donald Hupe

Research output: Contribution to journalArticle

Abstract

Normal connective tissue remodeling requires a family of enzymes called matrix metalloproteinases (MMPs) such as collagenases, gelatinases, and stromelysins. Excess activity of these proteinases often leads to pathological conditions such as arthritis, neural degenerative diseases, and periodontal diseases by uncontrolled degradation of extracellular matrix components. One of the therapeutical approaches is to develop inhibitors for these enzymes to restore the control on the enzymatic activities. MMPs are homologous enzymes with defined domain structures. We expressed the catalytic domains of human MMPs in E. coil and used these recombinant catalytic domains in MMP inhibitor discovery. We obtained initial inhibitors through random mass screening and demonstrated that inhibitors for the catalytic domains also inhibit corresponding full length MMPs. By combined use of chemical compound library screening, enzyme/inhibitor complex structural analysis, and inhibitor structural modification, we have obtained novel and non-peptidic MMP inhibitors with promising activities in animal diseases models.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997
Externally publishedYes

Fingerprint

Matrix Metalloproteinase Inhibitors
metalloproteinases
Matrix Metalloproteinases
active sites
Catalytic Domain
Enzyme Inhibitors
Screening
enzyme inhibitors
Small Molecule Libraries
Animal Disease Models
Matrix Metalloproteinase 3
Gelatinases
Mass Screening
Chemical compounds
Periodontal Diseases
Collagenases
Enzymes
animal disease models
Structural analysis
Osteoarthritis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Discovering non-peptidic inhibitors for matrix metalloproteinases with their recombinant catalytic domains. / Ye, Qizhuang; Johnson, Linda; Hupe, Donald.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

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