Georgia Institute of Technology College of Sciences

Coralyne is a small crescent-shaped molecule known to intercalate duplex and triplex DNA. We report that coralyne can cause the complete and irreversible disproportionation of duplex poly(dT)*poly(dA). That is, coralyne causes the strands of duplex poly(dT)*poly(dA) to repartition into equal molar equivalents of triplex poly(dT)*poly(dA)*poly(dT) and poly(dA). Poly(dT)*poly(dA) will remain as a duplex for months after the addition of coralyne, if the sample is maintained at 4 degrees C. However, disproportionation readily occurs upon heating above 35 degrees C and is not reversed by subsequent cooling. A titration of poly(dT)*poly(dA) with coralyne reveals that disproportionation is favored by as little as one molar equivalent of coralyne per eight base pairs of initial duplex. We have also found that poly(dA) forms a self-structure in the presence of coralyne with a melting temperature of 47 degrees C, for the conditions of our study. This poly(dA) self-structure binds coralyne with an affinity that is comparable with that of triplex poly(dT)*poly(dA)*poly(dT). A Job plot analysis reveals that the maximum level of poly(dA) self-structure intercalation is 0.25 coralyne molecules per adenine base. This conforms to the nearest neighbor exclusion principle for a poly(dA) duplex structure with A*A base pairs. We propose that duplex disproportionation by coralyne is promoted by both the triplex and the poly(dA) self-structure having binding constants for coralyne that are greater than that of duplex poly(dT)*poly(dA).