Nucleic Acid with Guanidinium Modification Exhibits Efficient Cellular Uptake

Ohmichi, Tatsuo; Kuwahara, Masayasu; Sasaki, Naoki; Hasegawa, Masatoshi; Nishikata, Takahito; Sawai, Hiroaki; Sugimoto, Naoki

doi:10.1002/anie.200500904

Cited by 46 publications

(20 citation statements)

References 33 publications

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“…It has to be recalled at this point that artefacts of redistribution into the nucleus have been encountered with cationic CPP when chemical fixation was used [59]. The role of the guanidinium group on the cellular uptake of modified ON was also demonstrated with DNA analogues incorporating 5-[(6-guanidinohexylcarbamoyl)methyl] uracyle instead of thymine nucleobases [60]. Free cell uptake was monitored by fluorescence on fixed and unfixed HeLa cells.…”

Section: Cationic Amino and Guanidino Onmentioning

confidence: 99%

Chemical Modifications to Improve the Cellular Uptake of Oligonucleotides

Debart¹,

Abes²,

Deglane³

et al. 2007

CTMC

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Specific control of gene expression by synthetic oligonucleotides (ON) is now widely used for target validation but clinical applications are limited by ON bioavailability. Moreover, most currently used strategies for physical and chemical delivery cannot be easily implemented in vivo. This article reviews new strategies which appear promising for ON delivery. The first part deals with ON chemical modifications aiming at improving cellular uptake as for instance the grafting of cationic groups on the ON backbone. The second part concerns ON conjugation to cell penetrating peptides.

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Section: Cationic Amino and Guanidino Onmentioning

confidence: 99%

Chemical Modifications to Improve the Cellular Uptake of Oligonucleotides

Debart¹,

Abes²,

Deglane³

et al. 2007

CTMC

View full text Add to dashboard Cite

show abstract

“…Very recently, ONs with guanidinium modification attached to the nucleobases exhibited efficient cellular uptake. [37] Collectively, these studies suggest that the guanidinium groups are critical for transport through biological barriers. Although the mechanism responsible for transport mediated by guanidine-rich molecules is still controversial, the design of new ON analogues bearing guanidinium groups could be of interest.…”

Section: Introductionmentioning

confidence: 98%

Impact of the Guanidinium Group on Hybridization and Cellular Uptake of Cationic Oligonucleotides

et al. 2006

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The grafting of cationic groups to synthetic oligonucleotides (ONs) in order to reduce the charge repulsion between the negatively charged strands of a duplex or triplex, and consequently to increase a complex's stability, has been extensively studied. Guanidinium groups, which are highly basic and positively charged over a wide pH range, could be an efficient ON modification to enhance their affinity for nucleic acid targets and to improve cellular uptake. A straightforward post-synthesis method to convert amino functions attached to ONs (on sugar, nucleobase or backbone) into guanidinium tethers has been perfected. In comparison to amino groups, such cationic groups anchored to alpha-oligonucleotide phosphoramidate backbones play important roles in duplex stability, particularly with RNA targets. This high affinity could be explained by dual recognition resulting from Watson-Crick or Hoogsteen base pairing combined with cationic/anionic backbone recognition between strands involving H-bond formation and salt bridging. Molecular-dynamics simulations corroborate interactions between the cationic backbones of the alpha-ONs and the anionic backbones of the nucleic acid targets. Moreover, ONs with guanidinium modification increased cellular uptake relative to negatively charged ONs. The cellular localization of these new cationic phosphoramidate ONs is mainly cytoplasmic. The uptake of these ON analogues might occur through endocytosis.

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“…Previously, we demonstrated the usefulness of KOD DNA polymerases in enzymatic syntheses of base-modified DNAs and investigated their application in SELEX methods since 2001. [66][67][68][69][70][71][72][73][74][75][76][77][78] Therefore, we readily noticed that KOD-related DNA polymerases are also applicable DNA synthesis involving modified sugars. This knowledge is now being widely accepted among researchers engaged in relevant studies.…”

Section: '4'-bna/lna Aptamers Created By Selex Selectionmentioning

confidence: 99%