Characterization of high molecular weight impurities in synthetic phosphorothioate oligonucleotides.
Phosphorothioate oligonucleotides manufactured by standard phosphoramidite techniques using 2'-deoxyadenosine- or 2'-O-(2-methoxyethyl)-5-methylcytosine-loaded solid supports contain branched impurities consisting of two chains linked through the exocyclic amino group of the 3'-terminal nucleoside of one chain and the 3'-terminal hydroxyl group of another via a P(O)SH group. These impurities are not produced when a universal, non-nucleoside derivatized support is used.
Kurata
Christine
C
Isis Pharmaceuticals Inc., 1896 Rutherford Road, Carlsbad, CA 92008, USA.
Bradley
Kym
K
Gaus
Hans
H
Luu
Nhuy
N
Cedillo
Isaiah
I
Ravikumar
Vasulinga T
VT
Van Sooy
Kent
K
McArdle
James V
JV
Capaldi
Daniel C
DC
D044503:5-Methylcytosine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013873:Thionucleotides / Q000737:chemistry*
D003839:Deoxyadenosines; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D013873:Thionucleotides; C434331:phosphoramidite; D044503:5-Methylcytosine