Development of an efficient method for phosphorodiamidate bond formation by using inorganic salts.
Phosphorodiamidate morpholino oligonucleotides (PMOs) have been extensively applied in antisense strategies for gene regulation because of their high stability in serum and low toxicity. However, chain elongation of PMOs requires long reaction time because few efficient methods have been developed for the formation of phosphorodiamidate bonds. In this Letter, we examined the effect of various additives to improve the reaction efficiency for formation of the phosphorodiamidate bond in the synthesis of PMOs. The addition of certain inorganic salts to the reaction media was found to be more effective. Particularly, lithium bromide was the most effective reagent and led to considerable acceleration (ca. 10-fold improvement).
Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsutacho, Midoriku, Yokohama 226-8501, Japan.
Taro
T
Harakawa
Hirosuke
H
Tsunoda
Akihiro
A
Ohkubo
Kohji
K
Seio
Mitsuo
M
Sekine
D001965:Bromides / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018020:Lithium Compounds / Q000494:pharmacology*; D015394:Molecular Structure; D060172:Morpholinos / Q000138:chemical synthesis* / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*
D001965:Bromides; D018020:Lithium Compounds; D060172:Morpholinos; D012492:Salts; C040949:lithium bromide