The 2-(N-formyl-N-methyl)aminoethyl group as a potential phosphate/thiophosphate protecting group in solid-phase oligodeoxyribonucleotide synthesis.
[reaction in text] The 2-(N-formyl-N-methyl)aminoethyl deoxyribonucleoside phosphoramidite 1 has been synthesized and used in the solid-phase synthesis of an octadecathymidylic acid as a cost-efficient monomer for potential application in the preparation of therapeutic oligonucleotides. The 2-(N-formyl-N-methyl)aminoethyl group can be cleaved from oligonucleotides according to a unique thermolytic cyclodeesterification process at pH 7.0. In addition to being cost-effective, the use of 1 simplifies oligonucleotide postsynthesis processing by eliminating the utilization of concentrated ammonium hydroxide in oligonucleotide deprotection.
Grajkowski
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A
Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, Maryland 20892, USA.
Wilk
A
A
Chmielewski
M K
MK
Phillips
L R
LR
Beaucage
S L
SL
D000469:Alkaline Phosphatase / Q000378:metabolism; D064753:Ammonium Hydroxide; D002847:Chromatography, Agarose; D004591:Electrophoresis, Polyacrylamide Gel; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000737:chemistry / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000191:economics; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry
C428007:2-(N-formyl-N-methyl)aminoethyl deoxythymdine phosphoramidite; D006878:Hydroxides; D009838:Oligodeoxyribonucleotides; D064753:Ammonium Hydroxide; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D013936:Thymidine