A5018809376- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Radical Photochemical Reactions
- DNA and Nucleic Acid Chemistry
- Catalytic C–H Functionalization Methods
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Asymmetric Hydrogenation and Catalysis
- Chemical Synthesis and Analysis
- Control Systems and Identification
- Sulfur-Based Synthesis Techniques
- Fault Detection and Control Systems
- Lipid Membrane Structure and Behavior
- Virus-based gene therapy research
- Advanced Fluorescence Microscopy Techniques
- Radioactive element chemistry and processing
- Chemical Synthesis and Reactions
- Analytical Chemistry and Chromatography
- Neural Networks and Applications
- MicroRNA in disease regulation
- Carbohydrate Chemistry and Synthesis
- Computational Drug Discovery Methods
- Catalytic Cross-Coupling Reactions
- Oxidative Organic Chemistry Reactions
- Chemical Reactions and Isotopes
AstraZeneca (Sweden)
2014-2024
Huawei Technologies (Sweden)
2023
AstraZeneca (Singapore)
2018
Innovative Medicines Initiative
2018
University of Gothenburg
2001-2006
Göteborgs Stads
2005
Swedish Chemicals Agency
2004
KTH Royal Institute of Technology
1998-2003
Stockholm University
2003
Texas Tech University
2003
Delivery of exogenous mRNA using lipid nanoparticles (LNPs) is a promising strategy for therapeutics. However, bottleneck remains in the poor understanding parameters that correlate with endosomal escape versus cytotoxicity. To address this problem, we compared distribution six LNP-mRNA formulations diverse chemical composition and efficacy, similar to those used mRNA-based vaccines, primary human adipocytes, fibroblasts, HeLa cells. Surprisingly, found total uptake not sufficient predictor...
Abstract Samarium( II ) iodide is a one‐electron transfer reagent that has become highly appreciated as mild and selective reducing agent in recent years. It been found experimentally various additives co‐solvents largely control the reactivity of SmI 2 . This microreview provides an overview current knowledge agent, particular with increase its reactivity. The use proton sources covered, well effect co‐solvents. Furthermore, very powerful mixture /H O/amine also described. (© Wiley‐VCH...
Methods for tracking RNA inside living cells without perturbing their natural interactions and functions are critical within biology and, in particular, to facilitate studies of therapeutic delivery. We present a stealth labeling approach that can efficiently, with high fidelity, generate transcripts, through enzymatic incorporation the triphosphate tCO, fluorescent tricyclic cytosine analogue. demonstrate this by tCO up 100% positions 1.2 kb mRNA encoding histone H2B fused GFP (H2B:GFP)....
Pharmacokinetics (PK) of antisense oligonucleotides (ASOs) is characterized by rapid distribution from plasma to tissue and slow terminal elimination driven re-distribution tissue. Quantitative understanding PK RNA knockdown for various ASO chemistries, conjugations, administration routes critical successful drug discovery. Here, we report concentration-time profiles a gapmer with locked nucleic acid ribose chemistry in mouse liver, kidney, heart, lung after subcutaneous intratracheal...
The SmI(2)-mediated reductions of ketones, imines, and alpha,beta-unsaturated esters have been shown to be instantaneous in the presence H(2)O an amine THF. are not only fast quantitative by addition amine, but workup procedures also simplified. Competing experiments with SmI(2)/H(2)O/amine confirmed that could selectively reduced ketones or imines. Comparison analogue ligands showed nitrogen phosphorus superior oxygen sulfur these reductions. trialkylphosphine...
A highly fluorescent, non-perturbing, pentacyclic adenine analog was designed, synthesized, incorporated into DNA and photophysical evaluated.
Here it was investigated how oligonucleotide retention and selectivity factors are affected by electrostatic non-electrostatic interactions in ion pair chromatography. A framework derived describing depends on the potential generated ion-pair reagent concentration, co-solvent volume fraction, charge difference between analytes, temperature. Isocratic experiments verified that, separation problems concerning oligonucleotides of different charges, increases with increasing surface analyte...
Mixtures of SmI(2)/H(2)O/amine have been found to reduce alkyl halides more efficiently than SmI(2)/HMPA/alcohol mixtures at room temperature. Alkyl and aryl iodides were quantitatively reduced in <1 min bromides 10 min, while chlorides required 5 h for completion. Determination the reaction order Et(3)N reduction 1-chlorodecane showed that is one. Water was shown not participate rate-determining step this reduction. There a significant change UV-vis spectrum color SmI(2) upon addition...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTSmI2/Water/Amine Mediates Cleavage of Allyl Ether Protected Alcohols: Application in Carbohydrate Synthesis and Mechanistic ConsiderationsAnders Dahlén, Andreas Sundgren, Martina Lahmann, Stefan Oscarson, Göran HilmerssonView Author Information Department Chemistry, Göteborg University, SE-412 96 Göteborg, Sweden, Organic Stockholm SE-106 91 Stockholm, Sweden Cite this: Org. Lett. 2003, 5, 22, 4085–4088Publication Date (Web):October 1,...
The mixture of samarium diiodide, amine, and water (SmI2/H2O/Et3N) is known to be a particularly powerful reductant, but until now the limiting reducing power has not been determined. A series unsaturated hydrocarbons with varying half-wave reduction potentials (E(1/2) = -1.6 -3.4 V, vs SCE) have treated SmI2/H2O/Et3N YbI2/H2O/Et3N, respectively. All -2.8 V or more positive were readily reduced SmI2/H2O/Et3N, whereas all -2.3 using YbI2/H2O/Et3N. This defines values chemical YbI2/H2O/Et3N SCE.
A drug discovery program in search of novel 5-lipoxygenase activating protein (FLAP) inhibitors focused on driving a reduction lipophilicity with maintained or increased ligand lipophilic efficiency (LLE) compared to previously reported compounds led the AZD6642 (15b). Introduction hydrophilic tetrahydrofuran (THF) ring at stereogenic central carbon atom significant shift physicochemical property space. The structure-activity relationship exploration and optimization DMPK properties leading...
The kinetics of the SmI2/H2O/amine-mediated reduction 1-chlorodecane has been studied in detail. rate reaction is first order amine and 1-chlorodecane, second SmI2, zero H2O. Initial studies more than 20 different amines show a correlation between base strength (pKBH+) logarithm observed initial rate, agreement with Brønsted catalysis law. To obtain activation parameters, constant for was determined at temperatures (0 to +40 °C, ΔH⧧ = 32.4 ± 0.8 kJ mol-1, ΔS⧧ −148 1 J K-1 ΔG⧧298K 76.4 1.2...
Abstract Interbase FRET can reveal highly detailed information about distance, orientation and dynamics in nucleic acids, complementing the existing structure techniques. We here report first RNA base analogue pair, consisting of donor tCO non-emissive acceptor tCnitro. The ribonucleoside is synthesised incorporated into for time. This pair accurately reports average A-form RNA, its utility probing structural changes demonstrated by monitoring transition from A- to Z-form RNA. Finally,...
Abstract The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments reach cytosolic nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds increase functional delivery. So far, development these has hindered a lack high-resolution methods that correlate SSO trafficking activity. Here we present in-depth characterization two novel using combination...
The SmI2-H2O-amine mixture has been shown to be effective for intramolecular couplings providing diastereoselectivities of up 100% de in the coupling O-cyclohexenyliodophenol derivatives into heterocycles.
Abstract With the central role of nucleic acids there is a need for development fluorophores that facilitate visualization processes involving without perturbing their natural properties and behaviour. Here, we incorporate new analogue adenine, 2CNqA, into both DNA RNA, evaluate its nucleobase-mimicking internal fluorophore capacities. We find 2CNqA displays excellent photophysical in acids, highly specific thymine/uracil, maintains slightly stabilises canonical conformations RNA duplexes....
Here, we present the non-linear spectroscopic characterization of fluorescent nucleobase analogue 2CNqA as a monomer and inside an antisense oligonucleotide. Its applicability 2P reporter is demonstrated using live cell imaging.
AZD8233, a liver-targeting antisense oligonucleotide (ASO), inhibits subtilisin/kexin type 9 protein synthesis. It is phosphorothioated 3-10-3 gapmer with central DNA sequence flanked by constrained 2'-O-ethyl 2',4'-bridged nucleic acid (cEt-BNA) wings and conjugated to triantennary N-acetylgalactosamine (GalNAc) ligand at the 5'-end. Herein we report biotransformation of as given liver, kidney, plasma urine samples, after repeated subcutaneous administration humans, mice, rats, rabbits,...