Nucleic acids tend to fall into kinetically trapped unstable structures because of their conformational polymorphism.  Nucleic acid chaperones accelerate association of nucleic acids assemblies into the thermodynamically most stable conformations.  Here, we report that a cationic comb-type copolymer promotes tetramolecular quadruplex assembly from mixtures of two different G-rich sequences, 5'-TGGGGT-3' (TG4T) and 5'-TGGGGGT-3' (TG5T).  A 1:1 mixture of TG4T and TG5T mainly gave [TG4T?(TG5T)3], [(TG4T)2?(TG5T)2] and [(TG4T)3?TG5T] heteroquadruplexes when the mixture was annealed by cooling from 90�C to 4�C at 1.0�C/min.  At a cooling rate of 0.01�C/min the mixture mostly assembled into [TG4T]4 and [TG5T]4 homoquadruplexes, indicating that homoquadruplexes were thermodynamically more stable than heteroquadruplexes. In the presence of the copolymer, mainly homoquadruplexes were obtained at cooling rate of 1�C/min, suggesting that the copolymer promoted formation of the thermodynamically most stable structures.  These results show that the copolymer works as a DNA annealer that induces proper assembly of stable DNA structures from heterogeneous kinetically trapped mixtures of structures.

Annealing activity of cationic comb-type copolymers for DNA assembly

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.