Metal-mediated base pairing within the simplified nucleic acid GNA.
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.
Schlegel
Mark K
MK
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg, Germany.
Zhang
Lilu
L
Pagano
Nicholas
N
Meggers
Eric
E
D020029:Base Pairing / Q000187:drug effects*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003300:Copper / Q000494:pharmacology; D006018:Glycols / Q000737:chemistry*; D008670:Metals / Q000494:pharmacology*; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D009696:Nucleic Acids / Q000737:chemistry*; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry; D044366:Transition Temperature
D002614:Chelating Agents; D006018:Glycols; D008670:Metals; D009696:Nucleic Acids; D009711:Nucleotides; D011728:Pyridones; D003300:Copper