Exploring Sulfur Sites in Proteins via Triple-Resonance H-Detected Se NMR.

NMR spectroscopy has been applied to virtually all sites within proteins and biomolecules; however, the observation of sulfur sites remains very challenging. Recent studies have examined Se as a replacement for sulfur and applied Se NMR in both the solution and solid states. As a spin-1/2 nuclide, Se is attractive as a probe of sulfur sites, and it has a very large chemical shift range (due to a large chemical shift anisotropy), which makes it potentially very sensitive to structural and/or binding interactions as well as dynamics.

Site-Specifically Conjugated Single-Domain Antibody Successfully Identifies Glypican-3-Expressing Liver Cancer by Immuno-PET.

Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease.

Rapid C Hyperpolarization of the TCA Cycle Intermediate α-Ketoglutarate via SABRE-SHEATH.

α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-C,5-C,D]α-ketoglutarate with the future goal of utilizing its [1-C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites .

Multivalent Gd-DOTA Decorated Oligopeptide as Sensitive MRI Molecular Probes for Imaging of Brain Connectivity.

One of the most important goals of brain imaging is to define the anatomical connections within the brain. In addition to revealing normal circuitry, studies of neural connections and neuronal transport can show rewiring and degeneration following brain injury and diseases. In this work, a highly sensitive magnetic resonance imaging (MRI)-visible neural tracer that can be used to visualize brain connectivity is developed.

Synthesis of [1- C-5- C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate.

Isocitrate dehydrogenase 1 (IDH1) mutations that generate the oncometabolite 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG) have been identified in many types of tumors and are an important prognostic factor in gliomas. 2-HG production can be determined by hyperpolarized carbon-13 magnetic resonance spectroscopy (HP- C-MRS) using [1- C]-α-KG as a probe, but peak contamination from naturally occurring [5- C]-α-KG overlaps with the [1- C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1- C-5- C]-α-KG was synthesized.

Real-Time insight into in vivo redox status utilizing hyperpolarized [1-C] N-acetyl cysteine.

Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies.

Synthesis and evaluation of C-labeled 5-5-dimethyl-1-pyrroline-N-oxide aimed at in vivo detection of reactive oxygen species using hyperpolarized C-MRI.

Effective means to identify the role of reactive oxygen species (ROS) mediating several diseases including cancer, ischemic heart disease, stroke, Alzheimer's and other inflammatory conditions in in vivo models would be useful. The cyclic nitrone 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) is a spin trap frequently used to detect free radicals in vitro using Electron Paramagnetic Resonance (EPR) spectroscopy. In this study, we synthesized C-labeled DMPO for hyperpolarization by dynamic nuclear polarization, in which C NMR signal increases more than 10,000-fold.

Benzoylated ethyl 1-thioglycosides: direct preparation from per-O-benzoylated sugars.

D-Glucose, lactose, maltose, and melibiose were benzoylated with Bz(2)O-Et(3)N reagent to give fully benzoylated β products. Under the same conditions, D-mannose produced a mixture where the β-benzoate predominated. Treatment of the foregoing compounds with EtSH at slightly elevated temperature (50-60°C) in the presence of BF(3)·Et(2)O as a promoter gave the corresponding ethyl 1-thio glycosides in high yields.