title: Grafting MAP peptide to dental polymer inhibits MMP-8 activity.
abstract: Matrix metalloproteinases (MMPs) are a class of zinc and calcium-dependent endopeptidases responsible for degrading extracellular matrix (ECM) components. Their activity is critical for both normal biological function and pathological processes (Dejonckheere et al., Cytokine Growth Factor Rev 2011;22:73-81). In dental restorations, the release and subsequent acid activation of MMPs contributes to premature failure. In particular, MMP-8 accelerates degradation by cleaving the collagen matrix within the dentin substrate in incompletely infiltrated aged bonded dentin (Buzalaf et al., Adv Dent Res 2012;24:72-76), hastening the need for replacement of restorations. Therefore, development of a dental adhesive that better resists MMP-8 activity is of significant interest. We hypothesize that modification of the polymer surface with an inhibitor would disable MMP-8 activity. Here, we identify the metal abstraction peptide (MAP) as an inhibitor of MMP-8 and demonstrate that tethering MAP to methacrylate polymers effectively inhibits catalysis. Our findings indicate complete inhibition of MMP-8 is achievable using a grafting approach. This strategy has potential to improve longevity of dental adhesives and other polymers and enable rational design of a new generation of biocompatible materials.
authors.affiliation: Bioengineering Research Center, University of Kansas, Lawrence, Kansas, 66045-7609.
authors.forename: Namrata
authors.initials: N
authors.lastname: Dixit
authors.forename: Jenifer K
authors.initials: JK
authors.lastname: Settle
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ye
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Berrie
authors.forename: Paulette
authors.initials: P
authors.lastname: Spencer
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Laurence
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002384:Catalysis; D003738:Dental Cements / Q000737:chemistry*; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000737:chemistry*; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D003738:Dental Cements; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D020784:Matrix Metalloproteinase 8
keywords: MMP-8; dental adhesive; fluorescence assay; grafting; inhibitor; metal abstraction peptide