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 19 of 19 for “"DMPK"”.
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DMPK and myotonic dystrophy : effects of CTG trinucleotide expansion upon DMPK and their contribution to DM pathogenesis
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1998.
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Proteomic analysis of the function of DMPK, the myotonic dystrophy protein kinase
… a gene which encodes a serine threonine kinase, DMPK. The precise mechanism by which CTG repeat expansion causes the complex pathology of DM1 is under active investigation. Repeat expansion leads to a failure of transport of DMPK mRNA from nucleus to cytoplasm indicating that reduction in DMPK …
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Characterisation of phenol hydroxylase and its auxiliary proteins, DmpM and DmpK, from pseudomonas spl Strain CF600
… The oxygenase requires an accessory protein, DmpK, for diiron cluster assembly. This thesis describes the characterisation of DmpM, DmpK, and DmpLNO. DmpM was found to exist in two forms. DmpM purified from the native strain was active in stimulating phenol hydroxylase activity, whereas an …
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A role for RNA localization in the human neuromuscular disease myotonic dystrophy
… by a (CTG)n expansion in the DM kinase (DMPK) gene 3' untranslated region while DM2 has a mutation in a small presumptive RNA binding protein. These analyses were guided by disease characteristics and have provided insights to DM's cytopathology, cell biology and molecular genetics. …
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The molecular genetics of familial cardiomyopathy
… (DCM) (DCM 334), we identified a pathogenic DMPK c.1067C>T(p.P356L) variant in the proband and her affected father. We also screened a cohort of 542 cardiomyopathy probands though Sanger sequencing of the DMPK gene and identified the DMPK c.1477C>T(p.R493C) variant as a variant of unknown …
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Identification and investigation of RNA-binding ligands
… CUG RNA repeat expansion in the 3’-UTR of the DMPK gene that sequesters a key splicing regulator, MBNL1, preventing normal modulation of alternative splicing of a variety of genes. Targeting these repeats with small molecules could block the sequestration of MBNL1 and restore normal splicing …
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Development of therapeutic agents for myotonic dystrophy type 1
… of the Dystrophia Myotonica Protein Kinase (DMPK) gene on chromosome 19. The genetic basis of DM1 is that DMPK is transcribed into an mRNA transcript with an expanded CUG repeat, r(CUG)exp, which can form hairpin secondary structures. These hairpin structures sequester the muscleblind-like …
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Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues
… of the drug metabolism and pharmacokinetics (DMPK), toxicity and efficacy profile of the drug. A representative set of compounds in four different series was synthesized in which the 4-aminoquinoline ring was coupled with benzothiazole, benzimidazole, benzoxazole and pyridyl rings bearing …
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Molecular analysis of myotonic dystrophy type 1 patients with an unusual molecular diagnosis
… of a (CTG)n repeat within the 3’-UTR of the DMPK gene (19q13.3). Normal individuals contain between 5 and 35 CTG repeats, whereas the repeats in DM1 patients expand in the range of 50 to several thousands. Longer alleles are very unstable and generally always increase in size when transmitted …
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Design, synthesis, and biological activities of small molecules that target myotonic dystrophy
… of CTG repeats (CUGexp) in the 3'-UTR of the DMPK gene (DM1) and CCTG repeats (CCUGexp) in the intron 1 of the ZNP9 gene (DM2). The sequestration of muscleblind-like proteins (MBNL) by CUGexp or CCUGexp causes splicing defects in more than 100 pre-mRNAs, resulting in various disease …
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Preclinical Study of Potential Antiglioma Novel Tetrahydroisoquinoline Analogs: Pharmacokinetics and Mechanism of Action
… undergoing drug metabolism/pharmacokinetics (DMPK)-guided lead optimization. EDL-291 was result from structure modification of last generation compound EDL-155. Its preclinical pharmacokinetics were characterized in this dissertation project. In male Sprague Daley (SD) rats, after 10 mg/kg …
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RNA recognition: controlling RNA-protein complexes with small molecules
… of the Dystrophia Myotonica protein kinase (DMPK) gene. The disease is characterized by a waning of the muscles (muscular dystrophy), eye-lens opacity and myotonia. The pathogenic poly(CUG)RNA and poly(CCUG)RNA binds to and sequesters key proteins, such as MBNL1 (muscleblind-like protein 1), …
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Development of enforced stacked intercalators that target trinucleotide repeat mismatches in DNA
… of the dystrophia myotonica protein kinase (DMPK) gene. Extensive efforts have made it possible to elucidate its pathogenesis and mechanism of action. In this regard, numerous compounds have been developed that target the toxic repeating CUG RNA transcript (r(CUG)exp) and inhibit its …
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Standard and Anomalous Wave Transport Inside Random Media
… solution of the Dorokhov-Mello-Pereyra-Kumar (DMPK) equation gives the distribution of transmission.</p> <p>For wave transport in standard one dimensional random systems in which the average number of scatterers per unit length is a constant, we get the ensemble average of the logarithm of …
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QUANTITATIVE PROTEOMIC APPROACHES TO STUDY DRUG MECHANISM OF ACTION
… results reducing possible side effects. From the DMPK perspective for covalent inhibitors, in vitro and in vivo data extrapolation, to obtain human pharmacokinetic projection, can be challenging and numerous efforts have to be undertaken in developing methods to accurately and quantitively …
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Drug discovery for misfolding diseases using structure-based iterative learning
… a poor drug metabolism and pharmacokinetics (DMPK) profile, which are negative features that may be difficult to eliminate. To address this, the updated machine learning approach combines generative modelling and reinforcement learning to identify small molecules that perturb the kinetics of …
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I MICRORNA NELLE DISTROFIE MIOTONICHE
… of the dystrophia myotonica-protein kinase (DMPK) gene on chromosome 19q13.3. Recently, the expansion of a CCTG tetranucleotide repeat located in the intron of the zinc finger 9 (ZNF9) gene on chromosome 19q13.3 was identified as the mutation responsible for DM2. Both mutations lead to the …
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Optimization of Enantiopure tetrahydro-β-carbolines as Potent Antimalarials and Exploration of salicylic acid analogs for combating multidrug-resistant Neisseria gonorrhoeae
The emergence of drug resistance towards existing drugs is a constant challenge in the fight against many diseases including Malaria and gonorrhoeae. To evade resistance, new targets must be engaged, and to do that, new structural classes of anti-infective must be prepared and evaluated. During the …
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Hit to Lead Stage Optimization of Orally Efficacious β-Carboline Antimalarials
Malaria, a disease caused by the parasite Plasmodium, continues to be one of the deadliest diseases worldwide. The WHO reported over 627,000 deaths in 2020, and over 1 billion people are at risk of infection. Even though Artemisinin-based Combination Therapies (ACT) are the current standard of care …