Oligonucleotides containing 2'-O-[2-(2,3-dihydroxypropyl)amino-2-oxoethyl]uridine as suitable precursors of 2'-aldehyde oligonucleotides for chemoselective ligation.
2'-O-[2-(2,3-Diacetoxypropyl)amino-2-oxoethyl]uridine 3'-phosphoramidite was prepared and used in solid-phase synthesis to obtain oligonucleotides containing a 1,2-diol group, which may then be converted into a 2'-aldehyde group. The oligonucleotides were conjugated efficiently to various molecules by chemoselective ligation that involves an addition-elimination reaction between the 2'-aldehyde group and a suitable nucleophile, such as a hydrazine, a O-alkylhydroxylamine or an 1,2-aminothiol. The method was applied successfully to the conjugation of peptides to oligonucleotides at the 2'-position.
Zubin
Eugeny M
EM
Department of Chemistry, M.V. Lomonossov Moscow State University, 1 Leninskie Gory, Moscow 119992, Russia.
Stetsenko
Dmitry A
DA
Zatsepin
Timofei S
TS
Gait
Michael J
MJ
Oretskaya
Tatiana S
TS
D000447:Aldehydes / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism
D000447:Aldehydes; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D014529:Uridine