Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphoprotein appears to play an important role in the mineralization of dentin during tooth development and remineralization after demineralization by dental caries. To better understand this role, we describe the extraction and characterization of phosphoprotein from immature, human root apex dentin during and after EDTA demineralization. The extraction procedure included dissociation of the demineralized dentin matrix by guanidine hydrochloride (Gdn.HCl) followed by subsequent digestion with cyanogen bromide (CNBr) and collagenase. Characterization of these extracts included 'Stains-All' staining of SDS polyacrylamide gels (SDS-PAGE) and amino acid, protein and phosphorus analyses. The ability of these matrices to remineralize was determined by TEM and measuring calcium levels in the remineralized tissue by atomic absorption spectroscopy. The staining of SDS-PAGE gels and amino acid analysis showed that an intact phosphophoryn was extracted from the dentin of the immature apices during EDTA demineralization and that it had an apparent Mr approximately 140,000. In the subsequent extracts and digests, the phosphoprotein has a range of molecular weights, some of which may have been degraded products of the intact phosphoprotein. A greater quantity of phosphoprotein was found in the EDTA-demineralized dentin matrices than in dentin after Gdn.HCl, CNBr and collagenase digests. These EDTA-demineralized matrices also remineralized to a greater extent than those dissociated with Gdn.HCl. The differences in both the quantity and the quality, as defined by the amino acid residue profile, of the phosphoprotein in the sequential extracts of the root apex dentin may be important in affecting the ability of this tissue to remineralize.
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PMID:Phosphoprotein analysis of sequential extracts of human dentin and the determination of the subsequent remineralization potential of these dentin matrices. 970 61

A new series of hydroxamic acid-based matrix metalloproteinase (MMP) inhibitors containing a unique phosphinamide motif derived from D-amino acid was designed, synthesized, and tested for enzyme inhibition. Compounds with an R configuration at phosphorus were found to be potent MMP inhibitors while molecules with the S configuration were almost inactive. Structure-activity relationship studies of the series led to the discovery of the potent inhibitor 16 with IC50 = 20.5 nM and 24.4 nM against fibroblast collagenase (MMP-1) and stromelysin (MMP-3), respectively. The binding mode of this novel phosphinamide-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 16.
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PMID:Design and synthesis of phosphinamide-based hydroxamic acids as inhibitors of matrix metalloproteinases. 988 35

A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K(i) values against MMP-1, -3, -9, and TACE and also showed nanomolar IC(50) values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.
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PMID:New type of metalloproteinase inhibitor: design and synthesis of new phosphonamide-based hydroxamic acids. 1183 4

A novel series of phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered by structural modification of tetrahydroisoquinoline derivative 1b, which was extremely weak inhibitor of TACE. (S)-Isomer at the phosphorus atom (7b) displayed potent inhibition for TACE, while selectivity sparing MMP-1, -3, and -9.
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PMID:Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE). 1278 Nov 87

In bone, osteoblasts and chondrocytes synthesize matrix vesicles (MVs) that interact with collagen to initiate calcification. MVs have been identified in human calcified arteries but are poorly characterized. The objective of this study is to determine the role of annexins and fetuin-A in MV formation and activity during calcification in bovine vascular smooth muscle cells (BVSMCs). BVSMCs were treated with control or calcification (high phosphorus) media, and cellular MVs were isolated by collagenase digestion and secreted MVs were isolated from cultured media by ultracentrifugation. The results showed that alkaline phosphatase (ALP) activity was significantly increased in MVs from calcified BVSMCs compared with noncalcified BVSMCs, as was annexin II and VI content and (45)Ca uptake. We also determined that MVs from calcifying BVSMCs could mineralize type I collagen but not type II collagen in the absence of cells in a dose- and time-dependent manner. Blockade of annexin calcium channel activity by K201 significantly decreased ALP activity and reduced the ability of the MVs to subsequently calcify on collagen, whether the K201 was added during or after MV formation. Furthermore, cellular MVs had significantly increased ability to calcify on collagen compared with secreted MVs, likely because of their increased ALP activity and annexin II content but low fetuin-A content. In conclusion, our results suggest that mineralization in VSMCs requires both active MVs and an interaction of the MVs with type I collagen, and both steps require annexin activity.
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PMID:Annexin-mediated matrix vesicle calcification in vascular smooth muscle cells. 1859 35

37 patients with chronic hepatitis B and C were examined. Patients were divided into 3 groups depending on the degree of connective tissue dysplasia. We investigated: free and protein-bounded hydroxyproline, collagenase activity, total alkaline phosphatase and its bone fraction, creatinine, calcium and phosphorus content in the blood serum and urine. It has been found the dependence of collagen synthesis from the state of connective tissue. The higher is the degree of dysplasia, the more intensive is the process of collagen synthesis (P < 0.05). The index of corellation between protein-bounded and free fraction can be used as a biochemical marker for determination the stage of pathological process in the liver and for monitoring the effectiveness of therapy.
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PMID:[Biochemical indices of connective tissue metabolism in patients with chronic hepatitis B and C]. 2551 90

Remineralization of dentin during dental caries is of considerable clinical interest. Dentin matrix protein 1 (DMP1) is a non-collagenous calcium-binding protein that plays a critical role in biomineralization. In the present study, we tested if peptides derived from DMP1 can be used for dentin remineralization. Peptide pA (pA, MW = 1.726 kDa) and peptide pB (pB, MW = 2.185), containing common collagen-binding domains and unique calcium-binding domains, were synthesized by solid-phase chemistry. An extreme caries lesion scenario was created by collagenase digestion, and the biomineral-nucleating potential of these peptides was ascertained when coated on collagenase-treated dentin matrix and control, native human dentin matrix under physiological levels of calcium and phosphate. Scanning electron microscopy analysis suggests that peptide pB was an effective nucleator when compared with pA. However, a 1:4 ratio of pA to pB was determined to be ideal for dentin remineralization, based on hydroxyapatite (HA) morphology and calcium/phosphorus ratios. Interestingly, HA was nucleated on collagenase-challenged dentin with as little as 20 min of 1:4 peptide incubation. Electron diffraction confirmed the presence of large HA crystals that produced a diffraction pattern indicative of a rod-like crystal structure. These findings suggest that DMP1-derived peptides may be useful to modulate mineral deposition and subsequent formation of HA when exposed to physiological concentrations of calcium and phosphate.
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PMID:DMP1-derived peptides promote remineralization of human dentin. 2569 69

Elevated serum phosphorus is a major risk factor for vascular calcification, which is characterized by the presence of calcium phosphate deposits, mainly hydroxyapatite crystals. In vitro studies of phosphate-induced calcification show that vascular smooth muscle cells undergo calcification with features similar to those observed in pathological vascular calcification in vivo, including the presence of hydroxyapatite crystals. Here, we describe the double-collagenase digestion method for isolating vascular smooth muscle cells from aorta, and a method for inducing calcification in vitro using high phosphate concentration.
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PMID:Isolation and Culture of Aortic Smooth Muscle Cells and In Vitro Calcification Assay. 2644 85


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