- Synthesis and RNA-Binding Properties of Extended Nucleobases for Triplex-Forming Peptide Nucleic Acids
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Triple-helix formation, using Hoogsteen hydrogen bonding of triplex-forming oligonucleotides, represents an attractive method for sequence-specific recognition of double-stranded nucleic acids. However, practical applications using triple-helix-forming oligonucleotides and their analogues are limited to long homopurine sequences. The key problem for recognition of pyrimidines is that they present only one hydrogen-bond acceptor or donor group in the major groove. Herein, we report our first attempt to overcome this problem by using peptide nucleic acids (PNAs) modified with extended nucleobases that form three hydrogen bonds along the entire Hoogsteen edge of the Watson-Crick base pair. New nucleobase triples (five) were designed, and their hydrogen bonding feasibility was confirmed by ab initio calculations. PNA monomers carrying the modified nucleobases were synthesized and incorporated in short model PNA sequences. Isothermal titration calorimetry showed that these nucleobases had a modest binding affinity for their double-stranded RNA (dsRNA) targets. Finally, molecular modeling of the modified triples in PNA-dsRNA helix suggested that the modest binding affinity was caused by subtle structural deviations from ideal hydrogen-bonding arrangements or disrupted π-stacking of the extended nucleobase scaffolds.
- Kumpina, Ilze,Brodyagin, Nikita,Mackay, James A.,Kennedy, Scott D.,Katkevics, Martins,Rozners, Eriks
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p. 13276 - 13298
(2019/10/16)
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- Pyrimidine Non-Classical Cannabinoid Compounds and Related Methods of Use
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Disclosed are compounds of the formula I: wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.
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Page/Page column 9
(2009/12/05)
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- Pyridine Non-Classical Cannabinoid Compounds and Related Methods of Use
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wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.
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Page/Page column 7
(2009/12/05)
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- PYRIDAZINE COMPOUND AND USE THEREOF
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A pyridazine compound of the formula: has an excellent plant disease controlling effect.
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Page/Page column 40
(2008/12/07)
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- Piperidine and tetrahydropyridine derivatives
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A class of substituted piperidine and tetrahydropyridine derivatives, linked through the 4-position thereof via an alkylene chain to a fused bicyclic heteroaromatic moiety such as indolyl, and further substituted at the 1-position by an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl-alkyl, aryl-alkyl or heteroaryl-alkyl moiety, are selective agonists of 5-HT1 -like receptors, being potent agonists of the human 5-HT1Dα; receptor subtype whilst processing at least a 10-fold selective affinity for the 5-HT1Dα; receptor subtype relative to the 5-HT1Dβ; subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.
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