title: Synthesis, binding, nuclease resistance and cellular uptake properties of 2'-O-acetalester-modified oligonucleotides containing cationic groups.
abstract: We report on the synthesis and properties of oligonucleotides (ONs) with 2'-O-acetalester modifications containing cationic side chains in a prodrug-like approach. In the aim to improve cell penetration and nuclease resistance, various different amino- or guanidino-acetalester were grafted to 2'-OH of uridine and the corresponding phosphoramidites were incorporated into ONs. Introduction of 2'-O-(2-aminomethyl-2-ethyl)butyryloxymethyl (AMEBuOM) modification into 2'-OMe ONs leads to high resistance towards enzymatic degradation and to destabilization of duplexes with complementary RNA strand. Spontaneous uptake experiments of a twelve-mer containing ten 2'-O-AMEBuOM-U units into A673 cells showed moderate internalization of ON within the cells whereas substantial internalization of the corresponding lipophilic 2'-O-pivaloyloxymethyl ON was observed for the first time.
authors.affiliation: Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, UM Campus Triolet, Place E. Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Biscans
authors.affiliation: Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, UM Campus Triolet, Place E. Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Rouanet
authors.affiliation: UMR 8203 CNRS, Université Paris-Saclay, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Jean-Rémi
authors.initials: JR
authors.lastname: Bertrand
authors.affiliation: Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, UM Campus Triolet, Place E. Bataillon, 34095 Montpellier Cedex 05, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Vasseur
authors.affiliation: Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, UM Campus Triolet, Place E. Bataillon, 34095 Montpellier Cedex 05, France. Electronic address: christelle.dupouy@umontpellier.fr.
authors.forename: Christelle
authors.initials: C
authors.lastname: Dupouy
authors.affiliation: Department of Nucleic Acids, IBMM UMR 5247, CNRS-Université Montpellier-ENSCM, UM Campus Triolet, Place E. Bataillon, 34095 Montpellier Cedex 05, France. Electronic address: francoise.debart@umontpellier.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Debart
mesh_terms: D000818:Animals; D001483:Base Sequence; D002412:Cations / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D002417:Cattle; D002460:Cell Line; D004951:Esterification; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000737:chemistry; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012911:Snakes; D014529:Uridine / Q000737:chemistry
chemical_list: D002412:Cations; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D010727:Phosphoric Diester Hydrolases; D014529:Uridine
keywords: 2′-O-Acetalester; Cationic groups; Cell uptake; Nuclease resistance; Oligonucleotides