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The promise of the antisense approach to treat a variety of diseases with oligonucleotides and solutions to challenges that have been encountered in their development is attributable to chemical modification of the nucleic acid scaffold. Herein, we describe preliminary data regarding the synthesis of a novel C5-propynyl-ß-D-arabinouridine (araU^P) phosphoramidite and its incorporation into oligonucleotides. Substitution of araU^P in dT₁₈ results in minor stabilization of duplexes formed with RNA when modifications are placed consecutively and a uniformly modified araU^P 18-mer increases stability by 34 °C relative to DNA. The modified oligomer exhibits improved nuclease and serum stability when compared to DNA and duplexes formed between RNA and araU^P oligonucleotides are substrates for E. coli RNase H. These preliminary results merit further investigation into C5-propynyl modified arabino nucleic acids for potential therapeutic gene silencing applications.