Spectroscopic studies on the binding interaction of novel 13-phenylalkyl analogs of the natural alkaloid berberine to nucleic acid triplexes

In this study we have characterized the capability of six 13-phenylalkyl analogs of berberine to stabilize nucleic acid triplex structures, poly(rA)center dot 2poly(rU) and poly(dA)center dot 2poly(dT). Berberine analogs bind to the RNA and DNA triplexes non-cooperatively. As the chain length of the substitution increased beyond CH2, the affinity enhanced up to critical length of (CH2)(4), there after which the binding affinity decreased for both the triplexes. A remarkably stronger intercalative binding of the analogs compared to berberine to the triplexes was confirmed from ferrocyanide fluorescence quenching, fluorescence polarization and viscosity results. Circular dichroism results had indicated strong conformational changes in the triplexes on binding of the analogs. The analogs enhanced the stability of the Hoogsteen base paired third strand of both the triplexes while no significant change in the high-temperature duplex-to-single strand transitions was observed. Energetics of the interaction revealed that as the alkyl chain length increased, the binding was more entropy driven. This study demonstrates that phenylalkyl substitution at the 13-position of berberine increased the triplex binding affinity of berberine but a threshold length of the side chain is critical for the strong intercalative binding to occur. (C) 2013 Elsevier B.V. All rights reserved.