2'-O-Methyl oligoribonucleotides with four kinds of 2'-O-modified uridine derivatives were synthesised. Their duplex stability, hydration behavior and exonuclease resistance were studied by spectroscopic analyses and molecular dynamics simulations. Consequently, 2'-O-modification of the uridine residue with 2-carbamoylethyl or 2-(N-methylcarbamoyl)ethyl groups resulted in a significant improvement of the exonuclease resistance without the loss of duplex stability.