Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Dendritic Alkyl Chains on DNA Cages: A Geometry-Dependent Inter- or Intramolecular “Handshake”
The selective association of hydrophobic side-chains is a strong determinant of protein organization. We have observed a parallel mode of assembly in DNA nanotechnology. Firstly dendritic DNA amphiphiles (D-DNA) were synthesized (Carneiro et al. 2009) comprising an addressable oligonucleotide portion and a hydrophobic alkyl dendron at the 5’ terminus. DNA amphiphiles have gathered interest recently as they can self-assemble in aqueous media to form well defined micelles while also retaining the ability to hybridize to their complement (Kwak & Herrmann, 2011; Patwa, A. et al. 2011). Two variations of alkyl D-DNA were hybridized to the single-stranded edges of a DNA cube McLaughlin, C. K. et al. (2012). It was found that anisotropic organization of these hydrophobic domains on the 3D scaffold results in a new set of assembly rules; dependent on spatial orientation, number and chemical identity of the D-DNA on the cubic structure Edwardson T.G.W. et al. (2012). When four amphiphiles are organized on one cube face, the hydrophobic residues engage in an intermolecular “handshake” between two cubes, resulting in a dimer. When eight amphiphiles are organized on the top and bottom faces of the cube, they engage in a “handshake” inside the cube. Combining the highly specific recognition of the oligonucleotide sequence with the orthogonal association of hydrophobic moieties can lead to a variety of structures with such diverse applications as membrane anchoring, cell uptake, directed hydrophobic assembly and encapsulation and release of small molecules.
This research has been supported by NSERC, CFI, CSACS, CIHR and CIFAR.
Kwak, M. & Herrmann, A. (2011)Nucleic acid amphiphiles: Synthesis and self-assembled nanostructures. Chem. Soc. Rev. 40, 5745-5755.
Patwa, A. et al. (2011) Hybrid lipid oligonucleotide conjugates: Synthesis, self-assemblies and biomedical applications. Che.l Soc. Rev. 40, 5844-5854.
McLaughlin, C. K. et al. (2012) Three-dimensional organization of block copolymers on "DNA- minimal" scaffolds. J. Am. Chem. Soc. 134, 4280-4286.
Edwardson T.G.W. et al. (2012) Dendritic Alkyl Chains on DNA Cages: A Geometry-Dependent Inter- or Intramolecular "Handshake". Nature Chem. Paper under review.
Thomas G.W. Edwardson
Department of Chemistry