title: Synthesis and physicochemical properties of oligonucleotides built with either alpha-L or beta-L nucleotides units and covalently linked to an acridine derivative.
abstract: Modified deoxynucleosides 2'-deoxy-beta-L-uridine, beta-L-thymidine, alpha-L-thymidine, 2'-deoxy-beta-L-adenosine and 2'-deoxy-alpha-L-adenosine were synthesized and assembled as homooligomers, respectively: octa-beta-L-deoxyuridylates, octa beta-L and alpha-L-thymidylates and tetra beta-L and alpha-L-deoxyadenylates. These unnatural oligomers were then substituted with an acridine derivative. The binding studies of these modified oligonucleotides with D-ribo- and D-deoxyribopolynucleotides were carried out by absorption spectroscopy. While beta-L-d(Up)8m5Acr, beta-L-(Tp)8m5Acr, alpha-L-(Tp)8m5Acr did not interact with poly(rA) and poly(dA), beta-L-d(Ap)4m5Acr and alpha-L-d(Ap)4m5Acr did form double and triple helices with poly(rU) and poly(dT), respectively. Their stability towards nuclease digestion was studied through comparison with that of octa-beta-D-thymidylate and tetra beta-D-deoxyadenylate covalently linked to an acridine derivative. One endonuclease (nuclease P1 from Penicillium citrinum) and two exonucleases (a 3'-exonuclease from Crotalus durissus venom and a 5'-exonuclease extracted from calf thymus) were employed. beta-L- and alpha-L-oligomers demonstrate a high resistance toward nuclease digestion.
authors.affiliation: Centre de Biophysique Moleculaire, CNRS, Orleans, France.
authors.forename: U
authors.initials: U
authors.lastname: Asseline
authors.forename: J F
authors.initials: JF
authors.lastname: Hau
authors.forename: S
authors.initials: S
authors.lastname: Czernecki
authors.forename: T
authors.initials: T
authors.lastname: Le Diguarher
authors.forename: M C
authors.initials: MC
authors.lastname: Perlat
authors.forename: J M
authors.initials: JM
authors.lastname: Valery
authors.forename: N T
authors.initials: NT
authors.lastname: Thuong
mesh_terms: D000166:Acridines / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D011071:Poly T / Q000378:metabolism; D011072:Poly U / Q000378:metabolism; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013053:Spectrophotometry; D013696:Temperature; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D000166:Acridines; D009841:Oligonucleotides; D011071:Poly T; D011072:Poly U; D005092:Exonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases; D000241:Adenosine; D013936:Thymidine; D014529:Uridine