Chemical synthesis of diastereomeric diadenosine boranophosphates (ApbA) from 2'-O-(2-cyanoethoxymethyl)adenosine by the boranophosphotriester method.
We have synthesized diastereomerically pure diadenosine 3',5'-boranophosphates (Ap(b)A) by using the boranophosphotriester method from ribonucleosides protected with the 2'-hydroxy protecting group 2-cyanoethoxymethyl (CEM). Melting curves of the triple-helical complex of the dimer Ap(b)A and 2poly(U) at high ionic strength revealed that presumptive (Sp)-Ap(b)A had a much higher affinity and presumptive (Rp)-Ap(b)A a much lower affinity for poly(U) than the natural dimer ApA did. In contrast, the affinities of these dimers for poly(dT) were similar. Both the (Rp)- and the (Sp)-boranophosphate diastereomers showed much higher resistance to digestion by snake venom phosphodiesterase and nuclease P1 than ApA did. They have potential for use as synthons to be incorporated into boranophosphate oligonucleotides. In particular, because oligonucleotides containing Sp boranophosphate nucleotides are expected to bind more strongly and specifically to RNA than natural oligoribonucleotides do, they may find application in the isolation and detection of functional RNA in basic research and diagnostics.
Enya
Yukiko
Y
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, 3-14-1 Sakura, Tsukuba City, Ibaraki 305-0003, Japan.
Nagata
Seigo
S
Masutomi
Yutaka
Y
Kitagawa
Hidetoshi
H
Takagaki
Kazuchika
K
Oka
Natsuhisa
N
Wada
Takeshi
T
Ohgi
Tadaaki
T
Yano
Junichi
J
D000241:Adenosine / Q000737:chemistry*; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D003486:Cyanides / Q000737:chemistry*; D004950:Esterases / Q000378:metabolism; D005019:Ethyl Ethers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010710:Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D001880:Boranes; D003486:Cyanides; D005019:Ethyl Ethers; D010710:Phosphates; C510710:boranophosphate; D004950:Esterases; D000241:Adenosine