4836-13-9Relevant articles and documents
Towards Zwitterionic Oligonucleotides with Improved Properties: the NAA/LNA-Gapmer Approach
Wojtyniak, Melissa,Schmidtgall, Boris,Kirsch, Philine,Ducho, Christian
, p. 3234 - 3243 (2020/09/01)
Oligonucleotides (ON) are promising therapeutic candidates, for instance by blocking endogenous mRNA (antisense mechanism). However, ON usually require structural modifications of the native nucleic acid backbone to ensure satisfying pharmacokinetic properties. One such strategy to design novel antisense oligonucleotides is to replace native phosphate diester units by positively charged artificial linkages, thus leading to (partially) zwitterionic backbone structures. Herein, we report a “gapmer” architecture comprised of one zwitterionic central segment (“gap”) containing nucleosyl amino acid (NAA) modifications and two outer segments of locked nucleic acid (LNA). This NAA/LNA-gapmer approach furnished a partially zwitterionic ON with optimised properties: i) the formation of stable ON-RNA duplexes with base-pairing fidelity and superior target selectivity at 37 °C; and ii) excellent stability in complex biological media. Overall, the NAA/LNA-gapmer approach is thus established as a strategy to design partially zwitterionic ON for the future development of novel antisense agents.
An efficient one-pot N-acylation of deoxy- and ribo-cytidine using carboxylic acids activated in situ with 2-chloro-4,6-dimethoxy-1,3,5-triazine
Rode, Ambadas B.,Son, Sang Jun,Hong, In Seok
experimental part, p. 2061 - 2064 (2010/11/19)
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Chelation-controlled regioselective alkylation of pyrimidine 2′-deoxynucleosides
Lucas,Teste,Zerrouki,Champavier,Guilloton
scheme or table, p. 199 - 207 (2010/03/23)
Protection-deprotection steps, which are usually needed for regioselective alkylation of pyrimidine deoxynucleosides, can be avoided by choosing the appropriate solvent. The combined effects of low dielectric constant and possible sodium chelation by pyrimidine nucleosides may account for the unexpected regioselectivity observed in THF.