A5076002630- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Acute Myeloid Leukemia Research
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Catalytic Reactions
- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Synthetic Organic Chemistry Methods
- RNA modifications and cancer
- Catalytic C–H Functionalization Methods
- Marine Toxins and Detection Methods
- Click Chemistry and Applications
- CRISPR and Genetic Engineering
- Catalytic Alkyne Reactions
- Nanowire Synthesis and Applications
- Bacterial biofilms and quorum sensing
- Biochemical and Molecular Research
- Glutathione Transferases and Polymorphisms
- Molecular Junctions and Nanostructures
University of Utah
2014-2023
Huntsman Cancer Institute
2012-2014
Howard Hughes Medical Institute
2006
Colorado State University
2001-2006
Western Washington University
2000-2004
Northwest University
2000-2004
Focusing on the Right Metabolite A variety of human cancers, including acute leukemias and brain tumors, have mutations in genes encoding isocitrate dehydrogenase 1 or 2 (IDH1, IDH2), which cause overproduction a metabolite called 2-hydroxyglutarate (2HG). Losman et al. (p. 1621 , published online 7 February) show that R - but not S -enantiomer 2HG can transform cells -2HG mediates transformation at least part through effects protein modifying EglN prolyl hydroxylases. Importantly,...
Human d-3-phosphoglycerate dehydrogenase (PHGDH), the first enzyme in serine biosynthetic pathway, is genomically amplified tumors including breast cancer and melanoma. In PHGDH-amplified cells, knockdown of PHGDH not fully rescued by exogenous serine, suggesting possible additional growth-promoting roles for enzyme. Here we show that, addition to catalyzing oxidation 3-phosphoglycerate, catalyzes NADH-dependent reduction α-ketoglutarate (AKG) oncometabolite d-2-hydroxyglutarate (d-2HG)....
Glucose and glutamine are abundant nutrients required for cell growth, yet how cells sense adapt to changes in their levels is not well understood. The MondoA transcription factor forms a heterocomplex with its obligate partner Mlx regulate ≈75% of glucose-dependent transcription. By mediating glucose-induced activation thioredoxin-interacting protein (TXNIP), MondoA:Mlx complexes directly repress glucose uptake. We show here that inhibits transcriptional TXNIP by triggering the recruitment...
Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated gene in grade II–III glioma and secondary glioblastoma (GBM). A causal role for IDH1R132H gliomagenesis has been proposed, but functional validation vivo not demonstrated. In this study, we assessed of development context clinically relevant cooperating genetic alterations vitro vivo. Immortal astrocytes expressing exhibited elevated (R)-2-hydroxyglutarate levels, reduced NADPH, increased proliferation, anchorage-independent...
Abstract A valuable pharmacophore , the 2‐aminoimidazole moiety, can be accessed with a variety of substitution patterns through an addition–hydroamination–isomerization sequence (see scheme; R 1 ,R 4 5 =alkyl; 3 =alkyl, aryl; 2 =H, alkyl, aryl). The synthesis propargyl cyanamide precursors three‐component coupling enables preparation this important heterocyclic core structure in just three steps. magnified image
Different than others: Dimeric rhodium(II) carboxylates uniquely catalyze the 6-endo-dig selective hydroamination of propargylguanidines while tranditional π-Lewis acids are typically 5-exo-dig (see scheme, oct=octanoate). Furthermore, this represents a new role for RhII to activate alkynes addition chemistry. Detailed facts importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by...
A concise stereoselective total synthesis of (+)-saxitoxin is described. silver(I)-initiated hydroamination cascade constructs the bicyclic guanidinium ion core from a alkynyl bisguanidine. This sequence creates two C–N bonds, one C–O bond, and three rings forms single stereoisomer in synthetic transformation. process enabled us to complete 14 steps N-Boc-l-serine methyl ester.
Scope Lipotoxicity‐induced endothelial dysfunction is an important vascular complication associated with diabetes. Clinical studies support the benefits of blueberry anthocyanins, but underlying mechanism unclear. The hypothesis that metabolites anthocyanins attenuate lipotoxicity‐induced was tested. Methods and results Human aortic cells (HAECs) were treated for 6 h either: (i) parent (malvidin‐3‐glucoside cyanidin‐3‐glucoside); or (ii) (hydroxyhippuric acid, hippuric benzoic...
Abstract Oncogenic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur a wide range of cancers, including acute myeloid leukemia (AML) glioma. Mutant IDH enzymes convert 2-oxoglutarate (2OG) to (R)-2-hydroxyglutarate [(R)-2HG], an oncometabolite that is hypothesized promote cellular transformation by dysregulating 2OG-dependent enzymes. The only (R)-2HG target has been convincingly shown contribute mutant the tumor suppressor TET2. However, there ample evidence suggest other...
This review will focus on the ability of 2-aminoimidazole to occupy a unique subset chemical space which makes it an ideal pharmacophore for development small molecule collections discovery based research. These observations rely both use 2-aminoimidazoles as building blocks in medicinal chemistry well recent alkaloids from sponges genus Leucetta exhibit diverse range biological activities around relatively limited structural core. The preparation these compounds also be highlighted.
Naturally occurring! The cyanobacterial metabolite 7-deoxycylindrospermopsin has been synthesized and its natural occurrence confirmed by HPLC. Structural analysis protein-inhibition studies show that the uracil unit does not appear to adopt unconventional tautomeric structure (see scheme), as previously thought, oxygenation at C7 is required for inhibition of protein biosynthesis.
Syntheses of the reported structures kealiinines B and C have been executed. An intermolecular electrophile-induced cyclization a pendant arene on an ene-guanidine affords tetracyclic, oxidized naphthimidazole cores.
The CDC biofilm reactor is a robust culture system with high reproducibility in which biofilms can be grown for wide variety of analyses. Multiple material types are available as growth substrates, yet data from on biologically relevant materials scarce, particularly antibiotic efficacy against differentially supported biofilms. In this study, holders were modified to allow collagen, substrate. Susceptibility multiple antibiotics was compared between varying species collagen versus standard...
The Cu(I)-catalyzed cycloaddition of alkynes and azides (click reaction) provides a robust method for the construction macrocyclic small molecules via an intramolecular macrocycloaddition. A three-subunit system has been used to explore tolerance this macrocycloaddition variations stereochemistries substituents.
Abstract Ein wertvolles Pharmakophor , die 2‐Aminoimidazol‐Einheit, ist durch eine Reaktionssequenz aus Addition, Hydroaminierung und Isomerisierung mit vielfältigen Substitutionsmustern zugänglich (siehe Schema; R 1 ,R 4 5 =Alkyl; 3 =Alkyl, Aryl; 2 =H, Alkyl, Aryl). Die Synthese der Propargylcyanamid‐Vorstufen Dreikomponentenkupplung ermöglicht Herstellung dieses wichtigen heterocyclischen Strukturmotivs in nur drei Stufen. magnified image
Anders als die anderen: Dimere Rhodium(II)-carboxylate katalysieren auf einzigartige Weise 6-endo-dig-selektive Hydroaminierung von Propargylguanidinen, während gewöhnliche π-Lewis-Säuren 5-exo-dig-selektiv sind (siehe Schema, oct=Octanoat). Somit lassen sich Alkine durch RhII für Additionsreaktionen aktivieren. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available...
A simple and efficient one-pot method for the synthesis of monoprotected guanidines is presented. Treatment an acylcyanamide with chlorotrimethylsilane generates a reactive N-silylcarbodiimide capable guanylating variety amines. Typically reaction complete in 15 min primary secondary aliphatic amines at rt. Hindered anilines are also competent nucleophiles but require extended times.
A synthetic strategy to establish five contiguous stereocenters, in a stereocontrolled manner, on the core structure of pactamycin is described. This sequence exploits use Lewis acid mediated epoxide opening cascade set relative configuration C4–C5 diol while reversing at C7. provides oxygenated just 11 steps.