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.
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).
Pradeepkumar
Pushpangadan I
PI
Contribution from the Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, S-75123 Uppsala, Sweden.
Cheruku
Pradeep
P
Plashkevych
Oleksandr
O
Acharya
Parag
P
Gohil
Suresh
S
Chattopadhyaya
Jyoti
J
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
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