MMP-13 (collagenase 3), a member of the matrix metalloproteinase family of zinc dependent enzymes, has been identified as an important target for the treatment of rheumatoid arthritis (RA). This enzyme is known to efficiently degrade type II collagen, the main structural component in cartilage. Its expression has been shown to be upregulated in RA.The major structural difference observed among the MMP structures is the relative size and shape of the S1’ pocket and this pocket is significantly longer for MMP-13. On the basis of the extended nature of the MMP-13 S1’ pocket a potent and selective inhibitor for MMP-13 was designed, synthesized and screened in vitro on isolated enzymes.
Design of selective collagenase 3 (MMP-13) inhibitors as potential therapeutic agents in rheumatoid arthritis
NUTI, ELISA;ROSSELLO, ARMANDO
2009-01-01
Abstract
MMP-13 (collagenase 3), a member of the matrix metalloproteinase family of zinc dependent enzymes, has been identified as an important target for the treatment of rheumatoid arthritis (RA). This enzyme is known to efficiently degrade type II collagen, the main structural component in cartilage. Its expression has been shown to be upregulated in RA.The major structural difference observed among the MMP structures is the relative size and shape of the S1’ pocket and this pocket is significantly longer for MMP-13. On the basis of the extended nature of the MMP-13 S1’ pocket a potent and selective inhibitor for MMP-13 was designed, synthesized and screened in vitro on isolated enzymes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
