"oligonucleotides" . "GA13-26526S" . . "2013-02-01+01:00"^^ . "http://www.isvav.cz/projectDetail.do?rowId=GA13-26526S"^^ . . . "5'-specific phosphodiesterase" . " H-phosphinates" . . . . " monomers" . " siRNA" . " 2'" . " nucleotides" . " RNase H" . . . " solid phase synthesis" . "Novel DNA and RNA oligonucleotides with Phosphonothioate and Phosphonoamidate Internucleotide Linkages."@en . "Project is aimed at the synthesis of structurally diverse, isopolar phosphonate oligonucleotides (ONs) with the nuclease-stable, phosphonate-type internucleotide linkage as potential (i) tools for gene expression regulation (antisense ONs, siRNAs), (ii) agonists/antagonists of TLR9 receptor (CpG motif-containing ONs), and (iii) effectors of 2-5A system - agonists/antagonists of RNase L (2',5'-oligoriboadenylates) and inhibitors of the 2',5'-specific phosphodiesterase. A key part of the project is the synthesis of monomers which, upon incorporation into DNA and RNA ONs, give rise to the formation of so far unexplored phosphonothioate, phosphonoamidate, and phosphonothioamidate internucleotide linkages. Biological effects of synthesized ONs will be tested in vitro on recombinant enzymes, cell cultures, and animal models. Interactions of ONs on molecular level will be studied by spectroscopic and theoretical methods and the obtained knowledge will be correlated with those obtained on biological activity of new ONs with the aim to understand more deeply structure-activity relationships."@en . " 2-5A" . "6"^^ . " RNase L" . . " phosphonates" . "6"^^ . "Projekt je zam\u011B\u0159en na synt\u00E9zu strukturn\u011B diverzifikovan\u00FDch izopol\u00E1rn\u00EDch analog\u016F oligonukleotid\u016F (ON) s nukle\u00E1zov\u011B stabiln\u00ED internukleotidovou vazbou fosfon\u00E1tov\u00E9ho typu jako mo\u017En\u00FDch (i) n\u00E1stroj\u016F k ovlivn\u011Bn\u00ED exprese genomu (antisensn\u00ED ON a siRNA), (ii) agonist\u016F/antagonist\u016F receptoru TLR9 (ON s CpG motivem) a (iii) efektor\u016F tzv. 2-5A dr\u00E1hy - agonist\u016F/antagonist\u016F RNasy L (2',5'-oligoriboadenyl\u00E1ty) a inhibitor\u016F 2',5'-specifick\u00E9 fosfodiesterasy. Z\u00E1sadn\u00ED sou\u010D\u00E1st\u00ED projektu je synt\u00E9za monomer\u016F \u2013 nukleosid-2'(3')- a 5'-fosfon\u00E1t\u016F/fosfin\u00E1t\u016F, jejich\u017E inkorporace do DNA a RNA oligomer\u016F, vede ke vzniku izostern\u00EDch a neizostern\u00EDch fosfonothio\u00E1tov\u00FDch, fosfonoamid\u00E1tov\u00FDch a fosfonothioamid\u00E1tov\u00FDch internukleotidov\u00FDch vazeb, kter\u00E9 nebyly dosud v ON studov\u00E1ny. \u00DA\u010Dinky p\u0159ipraven\u00FDch ON budou testov\u00E1ny in vitro na rekombinantn\u00EDch enzymech, tk\u00E1\u0148ov\u00FDch kultur\u00E1ch a na zv\u00ED\u0159ec\u00EDch modelech. Interakce ON budou studov\u00E1ny na molekul\u00E1rn\u00ED \u00FArovni spektr\u00E1ln\u00EDmi a teoretick\u00FDmi metodami a nov\u00E9 poznatky budou korelov\u00E1ny s biologickou aktivitou nov\u00FDch ON s c\u00EDlem v\u011Bd\u011Bt v\u00EDce o vztaz\u00EDch mezi strukturou a biologickou aktivitou." . " CpG motif" . "2016-12-31+01:00"^^ . "1"^^ . . . "1"^^ . . . " phosphonoamidates" . "2014-04-18+02:00"^^ . " phosphonoamidites" . "0"^^ . . "oligonucleotides; phosphonates; phosphonoamidites, phosphonoamidates; phosphonothioates; H-phosphinates; nucleotides; monomers; solid phase synthesis; RNase H; RNase L; 2',5'-specific phosphodiesterase; 2-5A; CpG motif; siRNA; antisense"@en . . " phosphonothioates" . . "2015-04-23+02:00"^^ . "Nov\u00E9 DNA a RNA oligonukleotidy s fosfonothio\u00E1tov\u00FDmi a fosfonoamid\u00E1tov\u00FDmi internukleotidov\u00FDmi vazbami" . .