Functionalized oligoanthranilamides: modular and conformationally controlled scaffolds.

Abstract

This paper describes the use of functionalized oligoanthranilamides as conformationally controlled scaffolds for molecular recognition. Oligomers of anthranilamides are stabilized by the formation of intramolecular six-membered hydrogen bonds in a linear strand conformation. Onto alternate anthranilic acid units, we have attached di- or tripeptide recognition units with the potential to form intramolecular hydrogen bonds to an intercalated peptide strand. Using 1H NMR dilution experiments in CDCl(3), we have observed chemical shift changes that are consistent with the formation of an extended hydrogen bonded sheet dimer. We also demonstrate that the bis-alanine functionalized strands are able to form discrete hydrogen bonded complexes with dipeptide substrates and to bind hexanoyl alanylalanine selectively over its benzyl ester. In the presence of excess hydrogen bond donors and acceptors, the oligoanthranilamide strand retained its linear conformation, pointing to the potential of this modular design as a useful and stable scaffold for molecular recognition studies.