title: Spectroscopic studies on the binding interaction of novel 13-phenylalkyl analogs of the natural alkaloid berberine to nucleic acid triplexes.
abstract: In this study we have characterized the capability of six 13-phenylalkyl analogs of berberine to stabilize nucleic acid triplex structures, poly(rA)⋅2poly(rU) and poly(dA)⋅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.
authors.affiliation: Biophysical Chemistry Laboratory, Chemistry Division, CSIR - Indian Institute of Chemical Biology, Kolkata 700 032, India.
authors.forename: Debipreeta
authors.initials: D
authors.lastname: Bhowmik
authors.affiliation: Naxopharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese (MI), Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Buzzetti
authors.affiliation: Naxopharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese (MI), Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Fiorillo
authors.affiliation: Naxopharma srl, Via G. Di Vittorio, 70, 20026 Novate Milanese (MI), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lombardi
authors.affiliation: Biophysical Chemistry Laboratory, Chemistry Division, CSIR - Indian Institute of Chemical Biology, Kolkata 700 032, India. Electronic address: gskumar@iicb.res.in.
authors.forename: Gopinatha
authors.initials: G
authors.lastname: Suresh Kumar
mesh_terms: D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D011061:Poly A / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: C051802:triplex DNA; D001599:Berberine; D011061:Poly A; C015465:poly(dA); D012313:RNA; D004247:DNA
keywords: Berberine analogs; Binding; DNA triplex; Intercalation; RNA triplex; Spectroscopy