tert-Butyldithiomethyl (DTM), a novel hydroxyl protecting group, cleavable under reductive conditions, was developed and applied for the protection of 2'-OH during solid-phase RNA synthesis. This function is compatible with all standard protecting groups used in oligonucleotide synthesis, and allows for fast and high-yield synthesis of RNA. Oligonucleotides containing the 2'-O-DTM groups can be easily deprotected under the mildest possible aqueous and homogeneous conditions. The preserved 5'-O-DMTr function can be used for high-throughput cartridge RNA purification. 相似文献
The molecular geometry of strontium dichloride has been determined by high-temperature electron diffraction (ED) and computational techniques. The computation at the MP2 level of theory yields a shallow bending potential with a barrier of about 0.1 kcal mol(-1) at the linear configuration. The experimentally determined thermal average Sr--Cl bond length, r(g), is 2.625+/-0.010 A and the bond angle, angle-spherical(a), is 142.4+/-4.0 degrees . There is excellent agreement between the equilibrium bond lengths estimated from the experimental data, 2.607+/-0.013 A, and computed at different levels of theory and basis sets, 2.605+/-0.006 A. Based on anharmonic analyses of the symmetric and asymmetric stretching as well as the bending motions of the molecule, we estimated the thermal average structure from the computation for the temperature of the ED experiment. In order to emulate the effect of the matrix environment on the measured vibrational frequencies, a series of complexes with argon atoms, SrCl(2)Ar(n) (n=1-7), with different geometrical arrangements were calculated. The complexes with six or seven argon atoms approximate the interaction best and the computed frequencies of these molecules are closer to the experimental ones than those computed for the free SrCl(2) molecule. 相似文献
Ab initio computations performed on LaF3?Arn (n=1–21) complexes allow a quantification of the short‐range many‐body interactions arising in the argon matrix. It is shown that the molecular properties of LaF3 are strongly influenced by the embedding medium. The largest investigated cluster, LaF3?Ar21, resembles an hcp structure with the LaF3 molecule occupying the central substitutional site (see figure).
All‐organic nanostructured host–guest materials (see picture) show enhanced, tunable fluorescence due to a high concentration of dyes with controlled spatial and geometrical organization that allows controlled resonant energy transfer. Homogeneous films of deoxycholic acid host–guests, provide coatings that convert near‐UV light into blue light with an efficiency higher than that of the standard polymeric blends.
Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives para-toluensulfonamide and ortho-toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the 14N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for ortho-toluensulfonamide, the vibration–rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS and r0 structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation, retaining the eclipsed configuration with respect to the SO2 frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor. 相似文献
GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans, such as keratan-sulfate. With the aim of identifying new pharmacological chaperones for GM1 gangliosidosis, the synthesis of five new trihydroxypiperidine iminosugars is reported in this work. The target compounds feature a pentyl alkyl chain in different positions of the piperidine ring and different absolute configurations of the alkyl chain at C-2 and the hydroxy group at C-3. The organometallic addition of a Grignard reagent onto a carbohydrate-derived nitrone in the presence or absence of a suitable Lewis Acid was exploited, providing structural diversity at C-2, followed by the ring-closure reductive amination step. An oxidation-reduction process allowed access to a different configuration at C-3. The N-pentyl trihydroxypiperidine iminosugar was also synthesized for the purpose of comparison. The biological evaluation of the newly synthesized compounds was performed on leucocyte extracts from healthy donors and identified two suitable β-Gal inhibitors, namely compounds 10 and 12. Among these, compound 12 showed chaperoning properties since it enhanced β-Gal activity by 40% when tested on GM1 patients bearing the p.Ile51Asn/p.Arg201His mutations. 相似文献
Current therapy against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are based on the use of Remdesivir 1, Molnupiravir 2, and the recently identified Nirmatrelvir 3. Unfortunately, these three drugs showed some limitations regarding potency and possible drug–drug interactions. A series of derivatives coming from a decoration approach of the privileged scaffold s-triazines were synthesized and evaluated against SAR-CoV-2. One derivative emerged as the hit of the series for its micromolar antiviral activity and low cytotoxicity. Mode of action and pharmacokinetic in vitro preliminary studies further confirm the role as candidates for a future optimization campaign of the most active derivative identified with this work. 相似文献
A popular intermediary in the theory of artificial satellites is obtained after the elimination of parallactic terms from the \(J_2\)-problem Hamiltonian. The resulting quasi-Keplerian system is in turn converted into the Kepler problem by a torsion. When this reduction process is applied to unbounded orbits, the solution is made of Keplerian hyperbolae. For this last case, we show that the torsion-based solution provides an effective alternative to the Keplerian approximation customarily used in flyby computations. Also, we check that the extension of the torsion-based solution to higher orders of the oblateness coefficient yields the expected convergence of asymptotic solutions to the true orbit.
The colony-stimulating factor 1 receptor (CSF1R) is a protein kinase emerging as an attractive target with clinical relevance in cancer, CNS and inflammatory diseases. Molecular docking experiments followed by synthesis and structure–activity relationship have been used to identify low molecular weight structures as promising hits for lead optimization. These molecules are synthesized from a 4-chloro-6-iodo-pyrrolo[2,3-d]pyrimidine building block using Negishi and Suzuki–Miyaura cross-coupling reactions in high yields. Several inhibitors possessed excellent enzymatic potency, and the parent compound preferably binds to the autoinhibited form of CSF1R. Cellular and in vivo profiling indicate that further tuning of drug structure is needed prior to efficacy studies. 相似文献