Metal-mediated base pairing within the simplified nucleic acid GNA

Abstract

Hydroxypyridone and pyridopurine homo- and hetero-base pairs have been investigated in the context of duplex GNA (glycol nucleic acid). Phosphoramidites for automated GNA solid phase synthesis were synthesized economically in a few steps starting from commercially available enantiopure glycidol. Similar to their behavior in DNA, the hydroxypyridone and pyridopurine homo-base pairs display a metal-dependent base pairing, with the hydroxypyridone base pair exhibiting a preference for copper(II) ions and the pyridopurine a preference for nickel(II) ions. However, these metallo-base pairs show modulated properties in GNA with respect to metal-dependent pairing stabilities and metal selectivities. Most interestingly, the hydroxypyridone homo-base pair and hydroxypyridone-pyridopurine hetero-base pair are particularly well accommodated in the GNA duplex and form copper(II)-dependent base pairs that are more stable compared to a Watson-Crick A:T base pair at the same position by nearly 20 degrees C and 24 degrees C, respectively. The structure of the copper(II)-hydroxypyridone homo-base pair is discussed based on a recent metallo-GNA duplex crystal structure.