Cation-regulated self-association of "synapsable" DNA duplexes

The simple innovation of introducing a block of G.G mismatches into a Watson-Crick DNA duplex permits two such duplexes, under conditions of physiological temperature and salt, to "synapse" with one another at their G.G mismatch sites via guanine-quartet formation. The short quadruplex formed at the "synapsed" site necessarily has its strands in an antiparallel, or partially antiparallel orientation. We wished to test whether a different, and more stable, synapsis might be achieved if one of the two strands in the synapsable duplex had its domain of guanine residues in a reverse orientation to the rest of the strand, via 5'-5' and 3'-3' linkages. Such modified duplexes might synapse via the formation of the thermodynamically preferred parallel quadruplex. Our results indicate that such "parallel" and "antiparallel" synaptic events have dramatically different requirements for cations. We use chemical probing experiments to provide evidence for a kinetic model for this discrepancy. It may be possible to exploit the distinct properties of the above two kinds of synapsable duplexes for a variety of in vivo and in vitro applications.