title: Peptide-based selective inhibitors of matrix  metalloproteinase-mediated activities.
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.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Ndinguri
authors.forename: Manishabrata
authors.initials: M
authors.lastname: Bhowmick
authors.forename: Dorota
authors.initials: D
authors.lastname: Tokmina-Roszyk
authors.forename: Trista K
authors.initials: TK
authors.lastname: Robichaud
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D020782:Matrix Metalloproteinases; D015032:Zinc