First evaluation of acyloxymethyl or acylthiomethyl groups as biolabile 2'-O-protections of RNA.
[reaction: see text] Short oligo-U sequences containing 2'-O-acyloxymethyl or acylthiomethyl groups as biolabile 2'-O-protections of RNA have been synthesized. These modified homouridylates are deprotected upon cellular esterase activation to release the parent RNA. They exhibit exceptional resistance to nuclease degradation, and the evaluation of their pairing properties shows that the 2'-acyloxymethyl groups do not prevent the duplex dsRNA formation. These biolabile 2'-modifications overcome the first hurdle to turn oligoribonucleotides into candidates for RNA interference drugs.
Parey
Nora
N
Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR 5625 CNRS-UMII, CC008, Université Montpellier II, Pl. Eugène Bataillon, 34095 Montpellier Cedex 05, France.
Baraguey
Carine
C
Vasseur
Jean-Jacques
JJ
Debart
Françoise
F
D043182:Carboxylesterase / Q000378:metabolism; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D009843:Oligoribonucleotides / Q000138:chemical synthesis*; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
D009843:Oligoribonucleotides; D012313:RNA; D012260:Ribonucleases; D043182:Carboxylesterase; D008697:Methane