Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: Identification of 12 novel mutations

Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (ΔF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G → T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant ΔF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity.published_or_final_versio

In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

A thorough investigation of the challenging Pd-catalyzed fluorination of five-membered heteroaryl bromides is presented. Crystallographic studies and density functional theory (DFT) calculations suggest that the challenging step of this transformation is C–F reductive elimination of five-membered heteroaryl fluorides from Pd(II) complexes. On the basis of these studies, we have found that various heteroaryl bromides bearing phenyl groups in the ortho position can be effectively fluorinated under catalytic conditions. Highly activated 2-bromoazoles, such as 8-bromocaffeine, are also viable substrates for this reaction.National Institutes of Health (U.S.) (GM46059)National Science Foundation (U.S.) (Predoctoral Fellowship 2010094243)Amgen Inc

Ein einfaches Verfahren zur Herstellung anellierter Thiophene

A simple method for the synthesis of fused thiophenes by reaction of agr-carboxymethyl substituted cyclic ketones withLawesson-reagent is described. Considerations concerning the reaction mechanism are given

On the Synthesis of Isomeric Dithiophene Analogues of Phenathridine- N-oxides

Six of nine o,o\u27-formylnitrobithienyls have been synthesized by the tetrakis(triphenylphosphine)palladium(O)-catalyzed coupling of the three o-bromonitrothiophenes with two of the three o-formylthiopheneboronic acids with sodium carbonate or sodium bicarbonate as base and an ethylene glycol dimethyl ether-water mixture as solvent. In the reaction with 3-formyl-2-thiopheneboronic acid, the coupling was carried out by using triethylamine as base and N,N-dimethylformamide as solvent in an attempt to avoid the facile deboronation of 3-formyl-2-thiopheneboronic acid, but without success. Reduction of the o,o\u27-formylnitrobithienyls gave high yields of the N-oxides of the six isomeric dithienopyridines, which are analogues of phenanthridine-N-oxide. A direct synthesis of one of the dithienopyridines, dithieno[2,3-c:2\u27,3\u27-c]-pyridine, was achieved by the palladium(O)-catalyzed coupling of 2,3-dibromothiophene with 2-formyl-3-thiopheneboranic acid to 3-bromo-2\u27-formyl-2,3\u27- -bithienyl, which was transformed to the 3-azido-2\u27-formyl-2,3\u27- -bithienyl, which upon reduction with hydrogen sulfide underwent ring closure to the phenanthridine analogue

Molecular and supramolecular chemistry of mono- and di-selenium analogues of metal dithiocarbamates

This bibliographic review summarises the coordination chemistry of mono- and diselenium analogues of metal dithiocarbamate ligands, [RRꞌNCS2]-, as revealed by X-ray crystallography and spectroscopy (77Se NMR and infrared). The Se-ligands are usually chelating but, bridging modes, up to 4, are known. Reflecting the larger size, greater polarisability and presence of a polar-cap (-hole), selenium atoms are more likely to be involved in secondary-bonding (chalcogen-bonding) than sulphur when a competition exists. Isostructural relationships are established across the series in about one-third of the structures

High Physiological Omega-3 Fatty Acid Supplementation Affects Muscle Fatty Acid Composition and Glucose and Insulin Homeostasis in Obese Adolescents

Obese adolescents have high concentrations of saturated fatty acids and low omega-3 long-chain polyunsaturated fatty acids (LCUFAs) in plasma phospholipids. We aimed to investigate effects of omega-3 LCPUFA supplementation to obese adolescents on skeletal muscle lipids and glucose and insulin homeostasis. Twenty-five obese adolescents (14–17 years old, 14 females) completed a randomized double-blind crossover study supplying capsules containing either 1.2 g omega-3 LCPUFAs or placebo, for 3 months each with a six-week washout period. Fasting blood glucose, insulin, leptin, adiponectin, and lipids were measured. Intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp were performed, and skeletal muscle biopsies were obtained at the end of each period. The concentrations of EPA, DHA, and total omega-3 PUFA in muscle phospholipids increased in both sexes. In the females, omega-3 LCPUFA supplementation improved glucose tolerance by 39% (P = 0.04) and restored insulin concentration by 34% (P = 0.02) during IVGTT. Insulin sensitivity improved 17% (P = 0.07). In males, none of these parameters was influenced by omega-3 supplementation. Thus, three months of supplementation of omega-3 LCPUFA improved glucose and insulin homeostasis in obese girls without influencing body weight

A Novel and Expedient Approach to New Thiazoles, Thiazolo[3,2-a]pyridines, Dihydrothiophenes, and Hydrazones Incorporating Thieno[2,3-b]thiophene Moiety

This paper reports details about the synthesis of a series of novel functionalized symmetrical bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif. Bis-thiazole derivatives 2, 3a-c and thiazolo[3,2-a]pyridine derivatives 4a-c are achieved. The hitherto unknown dihydrothiophene derivatives 6a-d via bis-pyridimium salt 5 are obtained. Additionally, the novel hydrazonothieno[2,3-b]thiophene derivatives 10a-c are obtained via bis-tosylacetylthieno[2,3-b]thiophene derivative 9. All compounds are characterized by 1H-, 13C-NMR, GCMS, IR, and UV-vis spectrometry. These compounds represent a new class of sulfur and nitrogen containing heterocycles that should also be of interest as new materials