The construction of an A-switch, derived from the artificial nucleic acid called acyclic Butyl Nucleic Acid (BuNA) was accomplished. The phosphoramidite building blocks of (S)-BuNA were synthesized from (R)-aspartic acid. To demonstrate its use as an A-switch, a stretch of polyadenine nucleotides of (S)-BuNA was studied by circular dichroism (CD) and ultraviolet (UV) spectroscopy under neutral and acidic conditions. Acid-base titration revealed two state transitions at pH 4.8 and highly pH-dependent structural conformation reversibility. Thermal melting (Tm) studies suggest that at neutral pH, poly BuNA(A) is a weakly organized single strand, while at low pH it adopts a highly organized and rigid structure. Furthermore, MALDI-TOF-MS data revealed intermolecular interactions which led to the formation of an A-motif composed of a double helical structure. Since BuNA does not suffer from depurination under acidic conditions, this allowed us to determine the thermodynamic parameters of the A-motif. This is the first report of the construction of an A-switch using artificial nucleic acids. © 2013 The Royal Society of Chemistry.