Allosteric Control of Self-Assembly: Modulating the Formation of Guanine Quadruplexes through Orthogonal Aromatic Interactions

摘要

Aromatic interactions are critical noncovalent forces that help stabilize the self-assembly of oligonucleotide (ODN) structures including duplex and quadruplex DNA. Much current work has focused on the development of ODN-tethered affinity-enhancing groups that make intramolecular contact and further stabilize duplex DNA through additional aromatic interactions. Recently, Berova and co-workers have demonstrated that porphyrin macrocycles linked to the 5'-terminus of ODNs can be used to stabilize, non-complementary, non-Watson-Crick duplexes through aromatic interactions with the terminal base pairs. However, there has been no exploration of the potential of these ODN-linked synthetic units with more complex DNA aggregates, such as guanine quadruplexes which self-assemble through sequential stacking of metal-templated guanine quartets (Scheme 1 A). Given the importance of quadruplex structures in telomere stabilization, oncogene activation, regulation of the insulin gene, as well as in the development of structural and functional supramolecular assemblies, we were keen to introduce synthetic agents capable of stabilizing guanine quadruplexes through designed orthogonal aromatic interactions.