Controlling nucleic acid secondary structure by intercalation: effects of DNA strand length on coralyne-driven duplex disproportionation.
Small molecules that intercalate in DNA and RNA are powerful agents for controlling nucleic acid structural transitions. We recently demonstrated that coralyne, a small crescent-shaped molecule, can cause the complete and irreversible disproportionation of duplex poly(dA)*poly(dT) into triplex poly(dA)*poly(dT)*poly(dT) and a poly(dA) self-structure. Both DNA secondary structures that result from duplex disproportionation are stabilized by coralyne intercalation. In the present study, we show that the kinetics and thermodynamics of coralyne-driven duplex disproportionation strongly depend on oligonucleotide length. For example, disproportionation of duplex (dA)16*(dT)16 by coralyne reverts over the course of hours if the sample is maintained at 4 degrees C. Coralyne-disproportioned (dA)32. (dT)(32), on the other hand, only partially reverts to the duplex state over the course of days at the same temperature. Furthermore, the equilibrium state of a (dA)16*(dT)16 sample in the presence of coralyne at room temperature contains three different secondary structures [i.e. duplex, triplex and the (dA)16 self-structure]. Even the well-studied process of triplex stabilization by coralyne binding is found to be a length-dependent phenomenon and more complicated than previously appreciated. Together these observations indicate that at least one secondary structure in our nucleic acid system [i.e. duplex, triplex or (dA)n self-structure] binds coralyne in a length-dependent manner.
Jain
Swapan S
SS
School of Chemistry and Biochemistry, Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Polak
Matjaz
M
Hud
Nicholas V
NV
D001600:Berberine Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011067:Poly dA-dT / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature
D001600:Berberine Alkaloids; D007364:Intercalating Agents; C051802:triplex DNA; D011067:Poly dA-dT; C000666:coralyne; D004247:DNA