Metalloproteinase inhibitors as therapeutics.
Matrix metalloproteinases (MMPs) are a family of enzymes which contain zinc at their active site and can degrade most of the matrix macromolecules found in connective tissues. These MMPs are secreted by connective tissue cells and infiltrating leucocytes in response to inflammatory mediators. There is now widespread recognition that MMPs are the major class of proteinases responsible for the excessive degradation of cartilage that leads to joint dysfunction in rheumatoid arthritis. The properties of the MMPs are reviewed and a therapeutic role for synthetic, zinc-binding pseudopeptide MMP inhibitors in the treatment of arthritis is proposed.
Gordon
J L
JL
British Bio-technology Limited, Oxford, U.K.
Drummond
A H
AH
Galloway
W A
WA
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D015195:Drug Design; D010450:Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018093:Gelatinases; D006801:Humans; D019278:Matrix Metalloproteinase 3; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D008969:Molecular Sequence Data
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010450:Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3