Investigation of the interactions of beta-peptides with DNA duplexes by circular dichroism spectroscopy

The interaction of beta-peptides with the DNA duplexes of dA(20)dT(20) and a GCN4-binding CRE sequence was examined. To gauge the factors that govern these interactions, two beta-pentadecapeptides, I and 2, a beta-dodecapeptide, 3, three beta-decapeptides, 4-6, three beta-heptapeptides, 7-9, and beta-octaarginine 10 were designed and synthesized. The beta-peptides were conceived to adopt a beta-peptide 3(14) helix, in which the side chains at position i and i + 3 are aligned vertically along one side of the helix. The side chains of Lys, Asn, and Arg were positioned such that potential H-bonding sites were created for a helical conformation to interact with the base pairs of DNA. CD Analysis showed that beta-peptides 1, 2, and 10 interacted with dA(20)dT(20). In addition, beta-peptides I and 2 showed significant interaction with a DNA-duplex 20mer containing the ATF/CREB recognition sequence for the regulatory protein GCN4. It is impossible, at this stage of the investigation, to make a safe proposal about the actual nature of the interaction of the structures(s) of the complexes, the formation of which is suggested by the CD spectra reported herein.