Collagenases design

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)... 

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... 

The HiTOPS device was recently used in the synthesis of combinatorial libraries of dike-topiperazines [61] for the development of highly selective inhibitors of collagenase-1. The HiTOPS system is easy to use, has an ergonomic design, and allows the use of up to 50 mg of a resin per well. The other advantage of this method is the commercial availability of the described devices. Affymax has licensed its technology to Whatman/Polyfiltronics, which manufactures the HiTOPS System. 

Islet isolation methods that yield islets free of contaminating fibroblasts now have been developed. Successful prevention of the growth of dense fibrous tissue on extravascular chambers containing these purified islets would raise new possibilities in the design of islet-transplantation chambers. This chapter contains the initial results of binding enzymes to Millipore AA cellulose ester membranes for application in such chambers. The enzyme chosen for study was collagenase from Clostridium histolyticum (Worthington Biochemicals, Inc.). 

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