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Medicinal-Pharmaceutical Chemistry Commons™
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Full-Text Articles in Medicinal-Pharmaceutical Chemistry
Meta-Analysis Reveals Both The Promises And The Challenges Of Clinical Metabolomics, Heidi E. Roth, Robert Powers
Meta-Analysis Reveals Both The Promises And The Challenges Of Clinical Metabolomics, Heidi E. Roth, Robert Powers
Chemistry Department: Faculty Publications
Clinical metabolomics is a rapidly expanding field focused on identifying molecular biomarkers to aid in the efficient diagnosis and treatment of human diseases. Variations in study design, metabolomics methodologies, and investigator protocols raise serious concerns about the accuracy and reproducibility of these potential biomarkers. The explosive growth of the field has led to the recent availability of numerous replicate clinical studies, which permits an evaluation of the consistency of biomarkers identified across multiple metabolomics projects. Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death and has the lowest five-year survival rate primarily due to the lack of an …
Nmr Metabolomics Protocols For Drug Discovery, Fatema Bhinderwala, Robert Powers
Nmr Metabolomics Protocols For Drug Discovery, Fatema Bhinderwala, Robert Powers
Chemistry Department: Faculty Publications
Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective and effective is a daunting proposition because disease biology is complex and highly variable across patients. Metabolomics enables the discovery of disease biomarkers, which provides insights into the molecular and metabolic basis of disease and may be used to assess treatment prognosis and outcome. In this regard, metabolomics has evolved to become an important component of the drug discovery process to resolve efficacy and toxicity issues, and as a tool for precision medicine. A detailed …
Structural Basis Of 7sk Rna 5′ Γ-Phosphate Methylation And Retention By Mepce, Yuan Yang, Catherine D. Eichhorn, Yaqiang Wang, Duilio Cascio, Juli Feigon
Structural Basis Of 7sk Rna 5′ Γ-Phosphate Methylation And Retention By Mepce, Yuan Yang, Catherine D. Eichhorn, Yaqiang Wang, Duilio Cascio, Juli Feigon
Chemistry Department: Faculty Publications
Among RNA 5′-cap structures, γ-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second non-enzymatic role as a core component of the 7SK RNP that is an essential regulator of RNA transcription. We report 2.0 and 2.1 Å X-ray crystal structures of human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5′ hairpin-single-stranded RNA region, explaining MePCE specificity for 7SK and U6. The structures reveal SAH and …
Structure And Function Of Preq1 Riboswitches, Catherine D. Eichhorn, Mijeong Kang, Juli Feigon
Structure And Function Of Preq1 Riboswitches, Catherine D. Eichhorn, Mijeong Kang, Juli Feigon
Chemistry Department: Faculty Publications
PreQ1 riboswitches help regulate the biosynthesis and transport of PreQ1 (7-aminomethyl-7- deazaguanine), a precursor of the hypermodified guanine nucleotide queuosine (Q), in a number of Firmicutes, Proteobacteria, and Fusobacteria. Queuosine is almost universally found at the wobble position of the anticodon in asparaginyl, tyrosyl, histidyl and aspartyl tRNAs, where it contributes to translational fidelity. Two classes of PreQ1 riboswitches have been identified (PreQ1-I and PreQ1-II), and structures of examples from both classes have been determined. Both classes form H-type pseudoknots upon PreQ1 binding, each of which has distinct unusual features and modes …