Book of Abstracts: Albany 2003
June 17-21 2003
Controlling Nucleic Acid Structural Transitions by Intercalation
We are investigating the ability for small molecule intercalation to drive nucleic acid structural transitions. We have recently shown that coralyne, a small crescent-shaped molecule, can cause complete and irreversible duplex disproportionation (1). That is, upon addition of coralyne, the strands of duplex poly(dT)·poly(dA) repartition into equal molar equivalents of triplex poly(dT)·poly(dA)·poly(dT) and single stranded poly(dA). We have also discovered that poly(dA) forms a duplex self-structure in the presence of coralyne, which is completely dependant on coralyne intercalation for stability. Similar investigations have now been carried out with homo-dT and homo-dA oligonucleotides of 16 and 32 nucleotides in length. We have found that duplex disproportionation by coralyne is profoundly dependant on oligonucleotide length. For example, disproportionation is reversible with temperature for dT16·dA16 over the course of hours, but requires days for dT32·dA32, and is apparently irreversible for poly(dT)·poly(dA). An equilibrium between three different secondary structures (i.e. duplex, triplex and the A·A duplex) can also be achieved at certain temperatures, depending upon oligonucleotide length. The interplay we observe between coralyne intercalation, temperature, and nucleic acid secondary structure reveals a complex system of intertwined thermodynamic and kinetic factors.
Swapan S. Jain*
School of Chemistry and Biochemistry