title: Synthesis, physicochemical and biochemical studies of 1',2'-oxetane constrained adenosine and guanosine modified oligonucleotides, and their comparison with those of the corresponding cytidine and thymidine analogues.
abstract: We have earlier reported the synthesis and antisense properties of the conformationally constrained oxetane-C and -T containing oligonucleotides, which have shown effective down-regulation of the proto-oncogene c-myb mRNA in the K562 human leukemia cells. Here we report on the straightforward syntheses of the oxetane-A and oxetane-G nucleosides as well as their incorporations into antisense oligonucleotides (AONs), and compare their structural and antisense properties with those of the T and C modified AONs (including the thermostability and RNase H recruitment capability of the AON/RNA hybrid duplex by Michaelis-Menten kinetic analyses, their resistance in the human serum, as well as in the presence of exo and endonucleases).
authors.affiliation: Contribution from the Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, S-75123 Uppsala, Sweden.
authors.forename: Pushpangadan I
authors.initials: PI
authors.lastname: Pradeepkumar
authors.forename: Pradeep
authors.initials: P
authors.lastname: Cheruku
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Plashkevych
authors.forename: Parag
authors.initials: P
authors.lastname: Acharya
authors.forename: Suresh
authors.initials: S
authors.lastname: Gohil
authors.forename: Jyoti
authors.initials: J
authors.lastname: Chattopadhyaya
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D001483:Base Sequence; D002942:Circular Dichroism; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000737:chemistry / Q000378:metabolism; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000378:metabolism; D009841:Oligonucleotides / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016914:Ribonuclease H / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D004988:Ethers, Cyclic; C000715470:MAS1 protein, human; D009692:Nucleic Acid Heteroduplexes; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D006151:Guanosine; D003562:Cytidine; D012313:RNA; D003850:Deoxyribonuclease I; D016914:Ribonuclease H; C005287:oxetane; D000241:Adenosine; D013936:Thymidine