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Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities
Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA
Department of Chemistry, Eastern Kentucky University, 521 Lancaster Avenue, Richmond, KY 40475, USA
Department of Periodontics, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Department of Biochemistry, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
* Author to whom correspondence should be addressed.
Received: 8 October 2012; in revised form: 20 November 2012 / Accepted: 28 November 2012 / Published: 30 November 2012
Abstract: The matrix metalloproteinases (MMPs) exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites), while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.
Keywords: matrix metalloproteinase; protease inhibitor; secondary binding site; cyclic peptide; phage display; triple-helix
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Ndinguri, M.W.; Bhowmick, M.; Tokmina-Roszyk, D.; Robichaud, T.K.; Fields, G.B. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities. Molecules 2012, 17, 14230-14248.
Ndinguri MW, Bhowmick M, Tokmina-Roszyk D, Robichaud TK, Fields GB. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities. Molecules. 2012; 17(12):14230-14248.
Ndinguri, Margaret W.; Bhowmick, Manishabrata; Tokmina-Roszyk, Dorota; Robichaud, Trista K.; Fields, Gregg B. 2012. "Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities." Molecules 17, no. 12: 14230-14248.