Abstract
Proflavine diazide (PD) with amido-azide substituents on the amine groups and its N-methylated analogue (MePD) bind strongly to DNA by nearest-neighbour intercalation with little sequence selectivity, presenting reactive azide groups in the major groove. PD is neutral in aqueous solution but experiences binding-coupled protonation on interaction with DNA with an apparent pKa shift of 2.5 units. MePD can be click modified in situ on DNA with alkyne-functionalised thienyl-pyrrole as a precursor for conducting polymer synthesis, and remains intercalated after reaction with the substituents aligned in the groove.
Highlights
The use of DNA as an architectural material was revolutionized by the seminal work of Seeman and coworkers in constructing 2D and 3D DNA nanostructures,[1] which resulted in an explosion of research in this field
The strong and well-characterized intercalative binding of acridines has led to their development as anticancer drugs,[10] and these properties make them attractive candidates for anchoring supramolecular architectures to a DNA scaffold
Searcey and coworkers produced a library of substituted acridine intercalators using click chemistry in solution,[13] one of which drove formation of Holliday junctions.13b 9-Aminoacridine azide was used for in situ click with an alkene peptide, where the reactants were pre-assembled.14a More recently, Balasubramanian and coworkers have used in situ click substitution of well-known tetraplex binders to identify drugs that bind selectively to G4 motifs.14b minor groove binding azido-ligands have been used for assembly of functional molecules on AT-rich DNA.14c In this paper we report the synthesis of novel proflavine derivatives with amidoazide substituents that intercalate DNA and undergo in situ click reactions[15] with molecules such as alkyne-substituted thienylpyrrole (TP)
Summary
The use of DNA as an architectural material was revolutionized by the seminal work of Seeman and coworkers in constructing 2D and 3D DNA nanostructures,[1] which resulted in an explosion of research in this field. Control of polymerization can be achieved by tethering monomers to DNA on the bases, sugars, or modified backbones.[7] we present first generation molecules for an alternative strategy which uses unmodified DNA as a scaffold to facilitate the linear assembly of functional materials. This strategy uses small molecules (ligands) that bind strongly to DNA with specific recognition modes (e.g. intercalation or groove binding)[8] to present reactive substituents in one DNA groove. The strong and well-characterized intercalative binding of acridines has led to their development as anticancer drugs,[10] and these properties make them attractive candidates for anchoring supramolecular architectures to a DNA scaffold
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