scholarly journals New Terpenoids from Chamaecyparis formosensis (Cupressaceae) Leaves with Modulatory Activity on Matrix Metalloproteases 2 and 9

Molecules ◽  
2018 ◽  
Vol 23 (3) ◽  
pp. 604 ◽  
Author(s):  
Meng-Lun Chang ◽  
Hui-Ching Mei ◽  
I-Chih Kuo ◽  
George Hsiao ◽  
Yueh-Hsiung Kuo ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1679
Author(s):  
Vishnu Mohan ◽  
Jean P. Gaffney ◽  
Inna Solomonov ◽  
Maxim Levin ◽  
Mordehay Klepfish ◽  
...  

Matrix metalloproteases (MMPs) undergo post-translational modifications including pro-domain shedding. The activated forms of these enzymes are effective drug targets, but generating potent biological inhibitors against them remains challenging. We report the generation of anti-MMP-7 inhibitory monoclonal antibody (GSM-192), using an alternating immunization strategy with an active site mimicry antigen and the activated enzyme. Our protocol yielded highly selective anti-MMP-7 monoclonal antibody, which specifically inhibits MMP-7′s enzyme activity with high affinity (IC50 = 132 ± 10 nM). The atomic model of the MMP-7-GSM-192 Fab complex exhibited antibody binding to unique epitopes at the rim of the enzyme active site, sterically preventing entry of substrates into the catalytic cleft. In human PDAC biopsies, tissue staining with GSM-192 showed characteristic spatial distribution of activated MMP-7. Treatment with GSM-192 in vitro induced apoptosis via stabilization of cell surface Fas ligand and retarded cell migration. Co-treatment with GSM-192 and chemotherapeutics, gemcitabine and oxaliplatin elicited a synergistic effect. Our data illustrate the advantage of precisely targeting catalytic MMP-7 mediated disease specific activity.


2016 ◽  
Vol 473 (11) ◽  
pp. 1471-1482 ◽  
Author(s):  
Lise Boon ◽  
Estefania Ugarte-Berzal ◽  
Jennifer Vandooren ◽  
Ghislain Opdenakker

Current knowledge about the glycosylation of matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) is reviewed. Whereas structural and functional aspects of the glycobiology of many MMPs is unknown, research on MMP-9 and MMP-14 glycosylation reveals important functional implications, such as altered inhibitor binding and cellular localization. This, together with the fact that MMPs contain conserved and many potential attachment sites for N-linked and O-linked oligosaccharides, proves the need for further studies on MMP glycobiology.


Author(s):  
Agnès Noël ◽  
Amin Hajitou ◽  
Cécile L'Hoir ◽  
Erik Maquoi ◽  
Eugénia Baramova ◽  
...  

Holzforschung ◽  
2009 ◽  
Vol 63 (1) ◽  
Author(s):  
Fang-Hua Chu ◽  
Pei-Min Kuo ◽  
Yu-Rong Chen ◽  
Sheng-Yang Wang

AbstractAnalyzing the gene sequences of terpene synthase (TPS) may contribute to a better understanding of terpenes biosynthesis and evolution of phylogenetic taxonomy.Chamaecyparis formosensisis an endemic and precious conifer of Taiwan. To understand the biosynthesis mechanism of terpenes in this tree, a full length of putative mono-TPS, named asCf-Pin(GeneBank accession no. EU099434), was obtained by PCR method and RACE extension. TheCf-Pinhas an 1887-bp open reading frame and encodes 628 amino acids. To identify the function ofCf-Pin,the recombinant protein fromEscherichia coliwas incubated with geranyl diphosphate, produced one major product, the structure of which was elucidated. GC/MS analysis and matching of retention time and mass spectrum with authentic standards revealed that this product isα-pinene. This is the first report of cloning of a mono-TPS and functionally expressed inE. coliand which could be identified asα-pinene synthase from a Cupressaceae conifer.


2008 ◽  
Vol 16 ◽  
pp. S156
Author(s):  
A. Gonzalez ◽  
C. Rodriguez-Fontenla ◽  
J. Rodriguez-Lopez ◽  
J. Loughlin ◽  
A. Tsezou ◽  
...  

MedChemComm ◽  
2011 ◽  
Vol 2 (10) ◽  
pp. 942 ◽  
Author(s):  
Ying Li ◽  
Richard Ting ◽  
Curtis W. Harwig ◽  
Ulrich auf dem Keller ◽  
Caroline L. Bellac ◽  
...  

2012 ◽  
Vol 90 (2) ◽  
pp. 141-153 ◽  
Author(s):  
Tatyana A. Korolenko ◽  
Fedor V. Tuzikov ◽  
Marina S. Cherkanova ◽  
Thomas P. Johnston ◽  
Natalia A. Tuzikova ◽  
...  

The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407-treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL1–3-C subfractions) and very low-density lipoprotein-C (VLDL-C) (VLDL1–2-C and VLDL3–5-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL2-C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL1–3-C subfraction), and the LDL1–3-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P-407.


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