Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 21 for “"binding conformation"”.
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Dibenzo-30-crown-10: Synthetic optimization and studies of the binding conformation
… Four new rotaxanes based on the DB30C10-paraquat binding motif were used to investigate the binding conformation of DB30C10 and paraquat. The new rotaxanes were characterized by 1H, 13C and 2D-NOESY NMR, mp, and HRMS. A single crystal X-ray structure of one of the [2]rotaxanes was obtained. To our …
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Synthesis and evaluation of β-fluoro-γ-aminobutyric acid enantiomers
… and in an overall yield of 31%. The preferred conformations of 3-fluoro-GABA in solution are then explored by NMR analysis and ab initio calculations. The biological evaluation of 3-fluoro-GABA enantiomers on GABA aminotransferase was then investigated and showed that the (R)-enantiomer …
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Synthesis and Biological Evaluation of Novel Epibatidine Analogues
… and bis-epibatidine derivative 3 exhibited high binding affinity relative to nicotine. In addition, a new series of 2-(hydroxyalkylpyridyl)-7-azabicyclo[2.2.1]heptane derivatives were synthesized and evaluated as potential ligands for nicotinic acetylcholine receptors. Moreover, two rigid …
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Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain
The ability to predict protein-ligand binding affinities is a difficult and elusive goal in the field of molecular recognition. Models exist to predict binding energetics; however, they are not always capable of considering the incidental events in ligand-binding due to the tendency of the Gibbs …
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Investigation of protein-protein interaction using atomic force microscopy
… spectroscopy (FS) technique to study protein binding and dissociation. FS measures the strength of the protein molecules bond with high resolution down to pico-Newton either on the surface of solid substrate or the membrane of living cells. However, the interpretation of force measurements of …
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Transient collagen triple-helix binding to membrane type 1 matrix metalloproteinase : interaction studies and NMR-guided structural docking
… side of the hemopexin domain as a potential THP binding exosite. Mutation of residues from this area impairs triple-helical peptidase activity of MMP-14. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Additionally, …
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Decompositions of Free Energies in Molecular Simulation
… is applied to small molecules and ligand-protein binding. In chapter 5, IFST is applied to decompose hydration free energy at the surface of a protein into hydration sites. From these sites, information is inferred about the binding conformation of two proteins GABARAP and the GABA-A receptor. In …
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Structural and Synthetic Studies of Bioactive Natural Products
… in preparation for studies of the tubulin-binding conformation of paclitaxel by REDOR NMR. A new macrocyclic A-nor-paclitaxel was also synthesized, and was found to have good cytotoxicity and improved tubulin-binding activity as compared with paclitaxel.
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Syntheses and Bioactivities of Targeted and Conformationally Restrained Taxol Analogs
… have attempted to elucidate the bioactive binding conformation of taxol on microtubules. Three models have been proposed for this conformation. The T-taxol conformation was proposed by Dr. Snyder based on electron crystallographic density and molecular modeling. In this dessertation, a …
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Engineering of the quorum quenching lactonase GcL for altered substrate specificity by rational design
… of GcL uncovered key positions in substrate binding cleft that interact with the AHL substrate’s acyl tail. These positions were used as targets for site saturation mutagenesis, and several mutants with altered substrate preference were identified in a screening step and confirmed with …
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Actin-like filament A (AlfA) and AlfA-driven plasmid segregation
… bacteria that can form filaments upon nucleotide binding and their involvement in various cellular processes including cell shape determination, cell division, and DNA segregation led to a reconsideration of the evolutionary history of life. Actin-like filament A (AlfA) is a bacterial actin …
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Computational Studies on R67 Dihydrofolate Reductase: An Investigation Into Its Unique Binding Patterns
… of the productive complex, this enzyme exhibits binding cooperativity. Unlike other allosteric enzymes which achieve binding cooperativity through conformational changes, this enzyme does not appear to undergo any backbone alterations upon ligand binding. Therefore, a different mechanism must be …
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Ligand-based design of dopamine reuptake inhibitors : fuzzy relational clustering and 2-D and 3-D QSAR modleing
… remains undiscovered, any attempt to model the binding of drug-like ligands to this protein must necessarily include strategies that use ligand information. For flexible ligands that bind to the DAT, the identification of the binding conformation becomes an important but challenging task. In the …
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Inhibition and inactivation of prostaglandin synthase-2 and horseradish peroxidase
… of the contribution of specific contacts to binding will be crucial to drug design. The results of an investigation of the thermodynamics of binding of a series of aromatic hydroxamic acid analogues to the archetypical peroxidase horseradish peroxidase (HRP) revealed the importance of …
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Design, Syntheses and Biological Activities of Paclitaxel Analogs
The conformation of paclitaxel in the bound state on the protein has been proposed to be the T-taxol conformation, and paclitaxel analogs constrained to the T-taxol conformation proved to be significantly more active than paclitaxel in both cytotoxicity and tubulin polymerization assays, thus …
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The development of stapled peptides as chemical tools to investigate activin A signalling and as antibacterial agents targeting MsbA-mediated efflux
… whereby a peptide is constrained into its binding conformation, presents a means by which some of the weaknesses of peptide therapeutics may be overcome. This thesis describes two projects in which stapled peptides were developed to investigate PPIs, and closely related helix-helix packing …
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Characterizations on bacterial photosynthesis and respiration with optical spectroscopy and magnetic resonance
… elongated hydrogen bonds to the semiquinone. The binding conformation of QA- is heterogeneous in the LM dimer, with more flexibility on the O1 carbonyl side. The selective labeling of methoxy and methyl with 13C shows that the dihedral angles of methoxy substituents on the semiquinone ring are no …
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Patterning planar surfaces with motor proteins: Towards spatial control over motile microtubules
… protein denaturation due to drying and conformational changes caused by mechanical stress. Given the large persistence length of microtubules their encounters with the boundaries of the nanotracks are limited to shallow approach angles. This way, the generated structures proved very …
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Design, Syntheses and Bioactivities of Androgen Receptor Targeted Taxane Analogs, Simplified Fluorescently Labeled Discodermolide Analogs, and Conformationally Constrained Discodermolide Analogs
… drug candidate. Understanding the bioactive conformation of discodermolide is important for drug development, but this task is difficult due to the linear and flexible structure of discodermolide. Indirect evidence for the orientation of discodermolide in the tubulin binding pocket can be …
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Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs
… aimed at understanding the biologically active conformation of paclitaxel bound on β–tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is described and the REDOR studies of this compound complexed to tubulin agrees with the hypothesis that palictaxel adopts …
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