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 33 for “"rational drug design"”.
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Study of the aryl hydrocarbon receptor as a target for rational drug design
<p>The aryl hydrocarbon receptor (AhR) heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) for transcriptional regulation. We generated three N-terminal deletion constructs of the human AhR of 12-24 KDa in size—namely D1 (aa 84-295), D2 (aa 84-192) and D3 (aa 191-295)—to …
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Computer-Aided Drug Design of G-quadruplex Structures: Harnessing Polarization for Rational Drug Design
… This dissertation focuses on improving the rational design of GQ-binding ligands by advancing computational methods that better capture the structural and electrostatic properties of GQs. Central to this effort is the use of the classical Drude oscillator polarizable force field model to …
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NMR, Crystallographic and Computational Investigations of Peptides, Proteins and Bisphosphonates: New Paradigms for Rational Drug Design
… approaches, an alternate route to develop a new drug would be to start with an existing one. There are many advantages to this strategy since in many cases the ""leads"" will be in current use in humans or will have been in clinical trials which greatly enhances the likelihood of them being safe …
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A FRET Investigation into Molecular Mechanisms of Cardiac Troponin Activation in Reconstituted Thin Filaments
… signaling pathways and other muscle types. Rational drug design can develop therapies to treat CM at the protein level. However, a detailed knowledge of how sarcomeric proteins regulate muscle contraction is required. Muscle contraction occurs through a cyclic interaction between actin thin …
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New Chemotherapeutic Approaches for the Treatment of Parasitic Protozoan Diseases
… The work presented in this thesis focuses on the design, synthesis, and screening (in vitro and in vivo) of bisphosphonates as a novel class of anti-parasitic agents. The infectious agents targeted in this study are Trypanosoma brucei, Trypanosoma cruzi, Toxoplasma gondii, Leishmania spp., and …
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Probing the HIV reverse-transcriptase enzyme with novel bifunctional HIV-1 RT inhibitors of the general formula (NRTI)-spacer-(NNRTI)
… transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two …
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Computational engineering of small molecules to treat infectious diseases
Rational drug design of small molecules has led to the development of robust therapeutics that are currently used in the clinic. However, key challenges remain in designing drugs against infectious disease targets that are susceptible to mutation. To achieve full clinical efficacy against …
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A single molecule study on the structural basis of ion selective permeation in voltage-gated sodium channels
… in lipid environments, which are vital for rational drug design. The bacterial NavAb channel is highly like its eukaryotic orthologs in structure, function, and pharmacological profiles, serving as an ideal model for biochemical characterizations. I purified the NavAb channel proteins and …
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Trpv5: Structure, Function And Drug Discovery
… for future studies including but not limited to rational drug design, molecular dynamics investigations and targeted biochemical probing.
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Understanding ligand binding, selectivity and functions on the G protein-coupled receptors: A molecular modeling approach
… structure provides a distinct advantage in the rational drug design process. The increasing number of available G protein-coupled receptor crystal structures has enabled utilization of a varied number of computational approaches for understanding the ligand-receptor interactions, ligand …
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Approaches to lead generation for idiopathic pulmonary fibrosis targets
… compounds as a treatment for IPF. Accordingly, a rational drug design approach was pursued with the aim of creating novel, simple molecules derived from these two progenitor compounds, whilst strategically retaining key pharmacophoric elements of AM095 and PF-8380 hypothesised to be crucial for …
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Structural and Dynamic Proximal Proteomic Analysis of TRPV2 Ion Channel Activation
… 2-APB and CBD, where we found key residues for drug binding around the flexible S4-S5 linker region. A conserved mechanism for channel opening was also established. In addition to channel opening mechanisms, another vital aspect in channel function is to identify TRPV2’s protein effectors and …
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A microscopic model of signal transduction mechanisms: olfaction
… repercussions, especially in the field of rational drug design. So in general the thesis proves the physical feasibility and potential of a novel and generic signaling model, and in particular looks at those processes in olfaction. The conjecture 'Could humans recognize odours through …
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Part A: Antimalarial agents modified at the C-16 position of artemisinin; Part B: Lead optimization of falcipain-2 and falcipain-3 inhibitors
… are currently considered the most effective drugs against drug resistant plasmodium falciparum. However, its undesired physicochemical proprieties have limited its usage. In order to improve its effectiveness, scientists around the world have developed novel methodology to synthesize …
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Sites of interaction between calcitonin-family peptides and their receptors
… Despite the broad pharmacological potential as drug targets for treatments of diseases such as diabetes, migraine and osteoporosis, the calcitonin peptide family receptors are not fully characterised. This is mainly due to the difficulty in the structural determination and the complexity of the …
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Barriers to tuberculosis drug discovery: the mycobacterial cell wall
… resistance to several anti-tuberculosis drugs, making it critical in the success of Mycobacterium tuberculosis infection. Multiple layers encapsulate the cell membrane, including arabinogalactan chains and mycolic acids that are covalently bonded to the peptidoglycan layer, resulting in a …
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Molecular mechanism of interactions between estrogen receptor and estrogen receptor selective genotoxins
… Our group has proposed a new scheme for a rational drug design. This scheme utilizes recent findings on the mechanism of cisplatin, the drug found to cure in excess of 93% of all testicular cancer cases. Cisplatin forms DNA adducts that are toxic. The toxicity of these adducts is enhanced …
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Design and synthesis of modified peptide antibiotics of the vancomycin family
… has a number of significant advantages as a drug therapy. It exploits a target that is not found in the host cells, the cell wall. It does this by inhibiting transpeptidation, which blocks murein biosynthesis, destabilising the cell wall and allowing the internal osmotic pressure of the cell …
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Tracing Androgen Metabolism With Inhibition Of Aromatase In Breast Cancer: In Vitro Studies And Clinical Correlates
… represents a highly successful example of rational drug design in hormone-responsive cancer. Aromatase inhibitors (AI) are approved as a first line of therapy in both primary and metastatic estrogen-receptor positive (ER+) breast cancer, and have been shown to be superior to tamoxifen at …
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Probing the HIV Reverse-Transcriptase enzyme with novel bifunctional HIV-1 RT inhibitors of the general formula (NRTI)-spacer-(NNRTI)
… transcriptase inhibitors have prompted the design of double-drugs combining these two entities with the aim of addressing the emergence of resistance as well as searching for synergism between the two drug target sites on HIV reverse transcriptase (RT). The strategy involves combining two …
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