| Impact of the guanidinium group on hybridization and cellular uptake of cationic oligonucleotides. | |
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MedLine Citation:
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PMID: 16518865 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Gaëlle Deglane; Saïd Abes; Thibaut Michel; Paul Prévot; Eric Vives; Françoise Debart; Ivan Barvik; Bernard Lebleu; Jean-Jacques Vasseur |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chembiochem : a European journal of chemical biology Volume: 7 ISSN: 1439-4227 ISO Abbreviation: Chembiochem Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-04-05 Completed Date: 2006-07-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100937360 Medline TA: Chembiochem Country: Germany |
Other Details:
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Languages: eng Pagination: 684-92 Citation Subset: IM |
Affiliation:
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LCOBS, UMR 5625 CNRS-UMII, CC 008, Université Montpellier II, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cations
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chemical synthesis,
chemistry,
pharmacology Cell Proliferation / drug effects Cells, Cultured DNA / chemistry, drug effects Guanidine / chemistry* Hela Cells Humans Models, Molecular Molecular Structure Oligonucleotides / chemical synthesis, chemistry*, pharmacokinetics* Protein Conformation RNA / chemistry, drug effects Structure-Activity Relationship Temperature |
| Chemical | |
Reg. No./Substance:
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0/Cations; 0/Oligonucleotides; 113-00-8/Guanidine; 63231-63-0/RNA; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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