134834-32-5Relevant academic research and scientific papers
Syntheses of Morpholine-Based Nucleotide Analogs for Hepatic siRNA Targeting and Stabilization
Hofmeister, Armin,Jahn-Hofmann, Kerstin,Brunner, Bodo,Helms, Mike W.,Metz-Weidmann, Christiane,Krack, Arne,Kurz, Michael,Li, Ziyu,Weitzenberg, Merle M.,Pflimlin, Elsa,Plettenburg, Oliver,Scheidler, Sabine
, p. 6838 - 6855 (2021)
A morpholine-based nucleotide analog was developed as a building block for hepatic siRNA targeting and stabilization. Attachment of an asialoglycoprotein-binding GalNAc ligand at the morpholine nitrogen was realized with different linkers. The obtained morpholino GalNAc scaffolds were coupled to the sense strand of a transthyretin-targeting siRNA and tested for their knockdown potency in vitro and in vivo. A clear structure-activity relationship was developed with regard to the linker type and length as well as the attachment site of the morpholino GalNAc moieties at the siRNA sense strand. Further, simple alkylation of the morpholine nitrogen led to a nucleotide analog, which increased siRNA stability, when used as a double 3′-overhang at the sense strand sequence. Combination of the best morpholino GalNAc building blocks as targeting nucleotides with an optimized stabilizing alkyl-substituted morpholine as 3′-overhangs resulted in siRNAs without any phosphorothioate stabilization in the sense strand and clearly improved the duration of action in vivo.
Determination of the absolute configurations of the anteiso acid moieties of glycoglycerolipid S365A isolated from Corynebacterium aquaticum
Akasaka, Kazuaki,Shichijyukari, Seiya,Meguro, Hiroshi,Ohrui, Hiroshi
, p. 1719 - 1722 (2002)
The absolute configurations of the two acid moieties, 12- methyltetradecanoate and 14-methylhexadecanoate, of glycoglycerolipid S365A isolated from Corynebacterium aquaticum were determined by an HPLC analysis after their conversion with the chiral fluore
Synthesis and biological evaluation of analogs of altohyrtin C (spongistatin 2)
Wagner, Carl E.,Wang, Qiang,Melamed, Alexander,Fairchild, Craig R.,Wild, Robert,Heathcock, Clayton H.
, p. 124 - 136 (2008)
Several structural analogs that contain only part of the altohyrtin structure have been prepared and compared with synthetic altohyrtin C (2) for in vitro cytotoxicity against human colon (HCT116) and ovarian (A2780) cell lines. Whereas altohyrtin C was f
Regulating competing supramolecular interactions using ligand concentration
Teunissen, Abraham J. P.,Paffen, Tim F. E.,Ercolani, Gianfranco,De Greef, Tom F. A.,Meijer
, p. 6852 - 6860 (2016)
The complexity of biomolecular systems inevitably leads to a degree of competition between the noncovalent interactions involved. However, the outcome of biological processes is generally very well-defined often due to the competition of these interaction
4,4,16-Trifluoropalmitate: Design, Synthesis, Tritiation, Radiofluorination and Preclinical PET Imaging Studies on Myocardial Fatty Acid Oxidation
Colombano, Alessandro,Dall'Angelo, Sergio,Kingston, Lee,Gr?nberg, Gunnar,Correia, Claudia,Passannante, Rossana,Baz, Zuri?e,Morcillo, Miguel ángel,Elmore, Charles S.,Llop, Jordi,Zanda, Matteo
, p. 2317 - 2331 (2020)
Fatty acid oxidation (FAO) produces most of the ATP used to sustain the cardiac contractile work, although glycolysis is a secondary source of ATP under normal physiological conditions. FAO impairment has been reported in the advanced stages of heart failure (HF) and is strongly linked to disease progression and severity. Thus, from a clinical perspective, FAO dysregulation provides prognostic value for HF progression, the assessment of which could be used to improve patient monitoring and the effectiveness of therapy. Positron emission tomography (PET) imaging represents a powerful tool for the assessment and quantification of metabolic pathways in vivo. Several FAO PET tracers have been reported in the literature, but none of them is in routine clinical use yet. Metabolically trapped tracers are particularly interesting because they undergo FAO to generate a radioactive metabolite that is subsequently trapped in the mitochondria, thus providing a quantitative means of measuring FAO in vivo. Herein, we describe the design, synthesis, tritium labelling and radiofluorination of 4,4,16-trifluoro-palmitate (1) as a novel potential metabolically trapped FAO tracer. Preliminary PET-CT studies on [18F]1 in rats showed rapid blood clearance, good metabolic stability – confirmed by using [3H]1 in vitro – and resistance towards defluorination. However, cardiac uptake in rats was modest (0.24±0.04 % ID/g), and kinetic analysis showed reversible uptake, thus indicating that [18F]1 is not irreversibly trapped.
An Intramolecular Iodine-Catalyzed C(sp3)?H Oxidation as a Versatile Tool for the Synthesis of Tetrahydrofurans
Br?se, Stefan,Koch, Vanessa
supporting information, p. 3478 - 3483 (2021/07/22)
The formation of ubiquitous occurring tetrahydrofuran patterns has been extensively investigated in the 1960s as it was one of the first examples of a non-directed remote C?H activation. These approaches suffer from the use of toxic transition metals in overstoichiometric amounts. An attractive metal-free solution for transforming carbon-hydrogen bonds into carbon-oxygen bonds lies in applying economically and ecologically favorable iodine reagents. The presented method involves an intertwined catalytic cycle of a radical chain reaction and an iodine(I/III) redox couple by selectively activating a remote C(sp3)?H bond under visible-light irradiation. The reaction proceeds under mild reaction conditions, is operationally simple and tolerates many functional groups giving fast and easy access to different substituted tetrahydrofurans.
OLIGONUCLEOTIDES CONTAINING NUCLEOTIDE ANALOGS
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Page/Page column 219, (2021/03/13)
The present disclosure relates to double-stranded oligonucleotides, including double-stranded oligonucleotides such as siRNAs, comprising a sense strand oligonucleotide and an antisense strand oligonucleotide, and wherein the antisense strand oligonucleotide comprises one or more nucleotide analogs of formula (I-A) which are neither the 5'-overhang nucleotide nor the 3'-overhang nucleotide of the said antisense strand oligonucleotide, and wherein a nucleotide analog of formula (I-A) is as described in the disclosure. Oligonucleotides containing these analogs have superior biological activity, for example, increased in vitro stability and improved in vivo potency especially improved off-target profiles. The improved oligonucleotides are useful for silencing (e.g., reducing or eradicating) the expression of a target gene.
NUCLEOTIDE PRECURSORS, NUCLEOTIDE ANALOGS AND OLIGOMERIC COMPOUNDS CONTAINING THE SAME
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Page/Page column 218, (2019/10/01)
The present disclosure relates to novel nucleotide precursors and nucleotide analogs that can be incorporated into oligonucleotides, including double-stranded oligonucleotides such as siRNAs. Oligonucleotides containing these analogs have superior biological activity, for example, increased in vitro stability and improved in vivo potency especially duration of action. The improved oligonucleotides are useful for silencing (e.g., reducing or eradicating) the expression of a target gene. In particular embodiments, this invention encompasses specific nucleotide analogs to be included in double-stranded RNAs (dsRNAs), and especially in siRNAs, that can hybridize to messenger RNAs (mRNAs) of interest, so as to reduce or block the expression of target genes of interest. The present compounds have general formula (I), wherein each of Ra, Rb, Rc and Rd is independently, H or a (C1-C6) alkyl group and B is a heterocyclic nucleobase.
Concise synthesis of hydroxy β -methyl fatty acid ethyl esters
Sakai, Yuki,Asakura, Yukiko,Morita, Mitsuhiro,Takahashi, Takashi
, p. 1195 - 1198 (2017/12/26)
Hydroxy β-methyl fatty acid ethyl esters bearing different carbon chain lengths and varying hydroxyl group positions were successfully synthesized from symmetric diols. These fatty acid derivatives are useful intermediates of chemical probes for metabolic
Concise synthesis of hydroxy β-methyl fatty acid ethyl esters
Sakai, Yuki,Asakura, Yukiko,Takahashi, Takashi,Morita, Mitsuhiro
, p. 1195 - 1198 (2018/05/02)
Hydroxy β-methyl fatty acid ethyl esters bearing different carbon chain lengths and varying hydroxyl group positions were successfully synthesized from symmetric diols. These fatty acid derivatives are useful intermediates of chemical probes for metabolic
