| Selective Triple-Helical Peptide Inhibitor of Metalloproteinases for the Treatment of Cancer and Arthritis 
Description The triple-helical conformation of collagen has long been recognized for its role in structural stabilization of connective tissue. The dissolution of the collagen triple-helix has thus been implicated in a variety of diseases, such as arthritis, that affect the structural integrity of various components of the body. Collagen also provides a barrier between tissues and cells. Destruction of this barrier plays a role in tumor cell invasion and the metastatic process. A family of metalloenzymes, the matrix metalloproteinases (MMPs), has been recognized for their ability to hydrolyze collagen (“collagenolytic” activity). The MMP family has thus been the subject of intense research efforts, in order to elucidate their mechanisms of action, and allow for rational design of effective and selective MMP inhibitors. A previously developed novel methodology for constructing synthetic triple-helical peptides (THPs) is now being applied to these synthetic proteins for the design and synthesis of triple-helical transition state analog inhibitors. These inhibitors feature a phosphonate ester or phosphinic moiety in place of the scissile bond. These groups have been shown previously to inhibit MMPs, but only recently have the methods been developed for their convenient incorporation within a peptide sequence by solid-phase methods. Potential Applications - Therapeutic for arthritis and cancer.
State of Technology Development and Commercialization Preliminary testing has been performed and this inhibitor is available for licensing. Further research is being conducted to decrease the sequence length that will in turn reduce manufacturing costs. 
Figure Above: Tetrahedral intermediate (boxed) and statine and phosphorus-based transition state analog inhibitors.
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Updated August 10, 2008 | 
