Inhibitor collagenase

The PL-catechin conjugate showed greatly amplified concentration-dependent inhibition activity against bacterial collagenase (ChC) on the basis of the catechin unit, which is considered to be due to effective multivalent interaction between ChC and the catechin unit in the conjugate. The kinetic study suggests that this conjugate is a mixed-type inhibitor for ChC. Hyaluronidase is an enzyme which catalyzes hydrolysis of hyaluronic acid and is often involved in a number... 

An advantage of NMR spectroscopy is the analysis of protein dynamics. Measurement and analysis of the relaxation parameters R1 R2, and the 15N NOE of 15N-labeled proteins leads to an order parameter (S2) that can describe the relative mobility of the backbone of the protein. Both collagenase-1 and stromelysin-1 have been studied either as inhibited complexes or the free protein [19, 52], Stromleysin-1 was studied with inhibitors binding to prime or nonprime subsites. Presence or absence of inhibitors in the nonprime sites had minor effects on the highly ordered structure of residues in these subsites, which are in contact with the... 

Moy FJ, Pisano MR, Chanda PK, Urbano C, Killar LM, Sung M-L, Powers R. Assignments, secondary structure and dynamics of the inhibitor-free fragment of human fibroblast collagenase. J Biomol NMR 1997 10 9-19. 

Bartoki N, Winkler FK, Williams DH, D Arcy A, Broadhurst MJ, Brown PA, Johnson WH, Murray EJ. Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. Nat Struct Biol 1994 1 106-110. 

Lovejoy B, Cleasby A, Hassell AM, Longley K, Luther MA, Weigl D, McGeehan G, McElroy AB, Drewry D, Lambert MH, Jordan SR. Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science 1994 263 375-377. 

Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KAM, Martin R, Van Watrt H, Browner MF. Crystal structures of MMP-1 and MMP-13 reveal the structural basis for selectivity of collagenase inhibitors. Nat Struct Biol 1999 6 217-221. 

Burger, D. et al., Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes Involvement of membrane-associated cytokines, Arthr. Rheum., 41, 1748, 1998. 

Inhibitors of human neutrophil collagenase and human stromelysin have been designed (577) which are based on previous classes of MMP inhibitors, iV-carboxyalkyl peptides (578, 579), and peptide-based hy-droxamic acids (117) (580, 581). The -CH3 and 2-phenylethyl groups are important for inhibition of MMP-3. The X-ray crystal structure of MMP-3 with bound 117 shows that the inhibitor chelates Zn(II)... 

Fig. 30. X-ray crystal structure of batimastat-human neutrophil collagenase complex, showing the inhibitor coordinated to the catalytic Zn(II) (PDBID 1JAQ). Adapted from (576).

KI3. Kossakouska, A. E., Urbanski, S. J., Huchcroft, S. A., and Edwards, R. R., Relationship between clinical aggressiveness of large cell immunoblastic lymphomas and expression of 92 kDa gelatinase (type IV collagenase) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Oncol. Res. 4, 233-240 (1992). 

Synthetic Inhibitors of Bacterial and Mammalian Interstitial Collagenases... 

INHIBITORS OF MAMMALIAN COLLAGENASES Non-substrate analogue inhibitors Substrate analogue inhibitors Phosphorus-based inhibitors Sulphur-based inhibitors Hydroxamate inhibitors tt-Carboxyalkyl inhibitors Miscellaneous inhibitors... 

In order to assess the potency of any putative collagenase inhibitor, one... 

While this is in principle a valid approach to collagenase inhibitor design, there is some question as to whether or not the assumptions on which this model is based are valid. Specifically, there are several reasons for challenging the assumption that collagenases prefer substrate conformations that mimic those found in collagen. First, an examination of a model of collagen... 

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