Nm23-H1 Blocks Cell Motility Independently Of Its Known Enzymatic Activities In A Cohort Of Human Melanoma Cells,
2010
University of Kentucky
Nm23-H1 Blocks Cell Motility Independently Of Its Known Enzymatic Activities In A Cohort Of Human Melanoma Cells, Joseph Robert Mccorkle
University of Kentucky Doctoral Dissertations
The metastasis suppressor gene NM23-H1 has been shown to possess three enzymatic activities including nucleoside diphosphate kinase, histidine-dependent protein kinase and 3’-5’ exonuclease activity. While these properties have been demonstrated in vitro using recombinant proteins, the contribution of these activities to suppression of metastatic dissemination is unknown. Site-directed mutagenesis studies were used to identify amino acid residues which are required for proper function of each enzymatic activity associated with H1, providing a platform for studying the importance of each function on an individual basis. To assess the relevance of these activities to melanoma progression, a panel of mutants harboring selective …
Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights,
2010
Technological University Dublin
Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden
Articles
Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …
The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes,
2010
Chapman University
The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes, Keun-Hang Susan Yang, Sehamuddin Galadari, Dmytro Isaev, Georg Petroianu, Toni S. Shippenberg, Murat Oz
Mathematics, Physics, and Computer Science Faculty Articles and Research
The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 …
Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target,
2010
Wayne State University
Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala
Wayne State University Dissertations
N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …
Preparation And Characterization Of Lyophilized Cyclodextrin Complexes Of A Hemisuccinate Ester Of Delta-9-Tetrahydrocannabinol For Transmucosal Delivery,
2010
University of Mississippi
Preparation And Characterization Of Lyophilized Cyclodextrin Complexes Of A Hemisuccinate Ester Of Delta-9-Tetrahydrocannabinol For Transmucosal Delivery, Sampada Bhaskar Upadhye
Electronic Theses and Dissertations
Delta-9- Tetrahydrocannabinol (THC) is the primary active ingredient of the plant Cannabis sativa (marijuana), responsible for the majority of the pharmacological effects. The most promising clinical applications of THC approved by the Food and Drug Administration (FDA) are for the control of nausea and vomiting associated with chemotherapy and for appetite stimulation of AIDS patients suffering from anorexia and wasting syndrome. The only dosage form currently approved by FDA is an oral, soft gelatin capsule (e.g. Marinol®). In addition, orally administered THC from Marinol® has shown slow and variable absorption due to low oral solubility and first pass metabolism. Our …
