title: Trivalent metal ions based on inorganic compounds with in vitro inhibitory activity of matrix metalloproteinase 13.
abstract: Collagenase-3 (MMP-13) inhibitors have attracted considerable attention in recent years and have been developed as a therapeutic target for a variety of diseases, including cancer. Matrix metalloproteinases (MMPs) can be inhibited by a multitude of compounds, including hydroxamic acids. Studies have shown that materials and compounds containing trivalent metal ions, particularly potassium hexacyanoferrate (III) (K3[Fe(CN)6]), exhibit cdMMP-13 inhibitory potential with a half maximal inhibitory concentration (IC50) of 1.3μM. The target protein was obtained by refolding the recombinant histidine-tagged cdMMP-13 using size exclusion chromatography (SEC). The secondary structures of the refolded cdMMP-13 with or without metal ions were further analyzed via circular dichroism and the results indicate that upon binding with metal ions, an altered structure with increased domain stability was obtained. Furthermore, isothermal titration calorimetry (ITC) experiments demonstrated that K3[Fe(CN)6]is able to bind to MMP-13 and endothelial cell tube formation tests provide further evidence for this interaction to exhibit anti-angiogenesis potential. To the best of our knowledge, no previous report of an inorganic compound featuring a MMP-13 inhibitory activity has ever been reported in the literature. Our results demonstrate that K3[Fe(CN)6] is useful as a new effective and specific inhibitor for cdMMP-13 which may be of great potential for future drug screening applications.
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Shaanxi Alcohol Ether and Biomass Energy Engineering Research Center, Key laboratory of Yulin Desert Plants Resources, 229 Taibai North Road, Xi'an 710069, PR China.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Wen
authors.affiliation: College of Pharmacy, Nankai University, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: College of Pharmacy, Nankai University, PR China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Shaanxi Alcohol Ether and Biomass Energy Engineering Research Center, Key laboratory of Yulin Desert Plants Resources, 229 Taibai North Road, Xi'an 710069, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Shaanxi Alcohol Ether and Biomass Energy Engineering Research Center, Key laboratory of Yulin Desert Plants Resources, 229 Taibai North Road, Xi'an 710069, PR China; College of Pharmacy, Nankai University, PR China. Electronic address: xiang.liu@htmdc.org.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Shaanxi Alcohol Ether and Biomass Energy Engineering Research Center, Key laboratory of Yulin Desert Plants Resources, 229 Taibai North Road, Xi'an 710069, PR China; College of Pharmacy, Nankai University, PR China. Electronic address: yhshen@nwu.edu.cn.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Shen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002942:Circular Dichroism; D004795:Enzyme Stability / Q000187:drug effects; D005292:Ferricyanides / Q000737:chemistry* / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D020533:Angiogenesis Inhibitors; D005292:Ferricyanides; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C028033:potassium ferricyanide
keywords: Circular dichroism spectral; Collagenase-3 catalytic domain; Endothelial tube formation; Isothermal titration calorimetry; Metal ions; Protein refolding