An efficient kinetic resolution of primary propargylic amines with s-factors of up to 56 is reported. The strategy is based on a dual catalytic approach, namely the use of a newly developed and easy-to-make thiourea-amide anion binding catalyst in combination with 4-(dimethylamino)pyridine (DMAP), both employed at a 5 mol % catalyst loading. Benzylic amines are also resolved with s-factors of up to 38.
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http://dx.doi.org/10.1021/ja105337h | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China.
TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high-resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.
View Article and Find Full Text PDFMikrochim Acta
December 2024
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China.
An electrochemiluminescence (ECL) immunosensor was developed for the highly sensitive and specific detection of heart-type fatty acid binding protein (H-FABP) and the rapid diagnosis of acute myocardial infarction (AMI). H-FABP is a biomarker that is highly specific to cardiac tissue and is associated with a range of cardiac diseases. Following myocardial injury, the rate of increase in H-FABP levels is greater than that observed for myoglobin and troponin.
View Article and Find Full Text PDFMol Cell Endocrinol
December 2024
Amsterdam Institute for Life and Environment (A-Life), Vrije Universiteit Amsterdam (VU), De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Adequate levels of thyroid hormones (THs) in the fetal brain are vital for early neurodevelopment. Most of TH in fetal brain is derived from circulating thyroxine (T4), which gets locally converted into the biologically active triiodothyronine (T3) by deiodinase enzymes. One of the major routes of TH into the brain is through the blood-cerebrospinal fluid barrier (BCSFB).
View Article and Find Full Text PDFElectrophoresis
December 2024
Institute of Chemistry and Chemical Technology SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS", Krasnoyarsk, Russia.
An empirical equation relating electrophoretic mobility and ionic strength was proposed. The equation includes a number of parameters that are found using the mobilities of reference ions: two coefficients in the numerator describing the linear relationship of the multiplier in front of the square root of the ionic strength with the product of the ion mobility in the background electrolyte (BGE) without additives by the modulus of the charge number, raised to a certain power, and also the multiplier in the denominator before the square root of the ionic strength. The proposed equation was tested using the mobilities measured in BGEs with the addition of sodium chloride to adjust ionic strength and sulfated β-cyclodextrin (S-β-CD) for 11 anions with charge numbers from -1 to -4.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Ophthalmology, Columbia University, New York, NY, USA.
Best1 and Best2 are two members of the bestrophin family of anion channels critically involved in the prevention of retinal degeneration and maintenance of intraocular pressure, respectively. Here, we solved glutamate- and γ-aminobutyric acid (GABA)-bound Best2 structures, which delineate an intracellular glutamate binding site and an extracellular GABA binding site on Best2, respectively, identified extracellular GABA as a permeable activator of Best2, and elucidated the co-regulation of Best2 by glutamate, GABA and glutamine synthetase in vivo. We further identified multiple small molecules as activators of the bestrophin channels.
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