Core modified 8-17 DNAzymes with 2'-deoxy-2'-C-methylpyrimidine nucleosides.

Autor: Dellafiore M; Laboratorio de Química de Ácidos Nucleicos, INGEBI (CONICET), Ciudad Autónoma de Buenos Aires, Argentina., Montserrat JM; Instituto de Ciencias, Universidad Nacional de Gral. Sarmiento, Los Polvorines, Provincia de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Argentina. Electronic address: jmontser@campus.ungs.edu.ar., Iribarren AM; Laboratorio de Biotransformaciones, Universidad Nacional de Quilmes, Provincia de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Argentina. Electronic address: airibarren@unq.edu.ar.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Nov; Vol. 104, pp. 104328. Date of Electronic Publication: 2020 Sep 29.
DOI: 10.1016/j.bioorg.2020.104328
Abstrakt: The catalytic core of an 8-17 DNAzyme directed against STAT 3 was modified using (2'R) and (2'S) 2'-deoxy-2'-C-methyluridine and cytidine. While 2'-deoxy-2'-C-methyluridine significantly diminished the catalytic activity, 2'-deoxy-2'-C-methylcytidine replacement was better accepted, being the k act of modified DNAzymes at 8- and 11-positions comparable to the non-modified one. When 2'-O-methyl and phosphorothioate nucleotides were tested in the binding arms together with core modified DNAzymes the k cat was affected in a non predictable way, emphasizing the fact that both chemical substitutions should be considered globally. Finally, 2'-deoxy-2'-C-methyl modified DNAzymes stability was assayed finding that the double 2'-C-methyl modification in the catalytic core enhanced 70% the stability against a T47D cell lysate compared to a non-modified control.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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