Biophysical characterization of the strong stabilization of the RNA triplex poly(U)•poly(A)*poly(U) by 9-O-(ω-amino) alkyl ether berberine analogs.
BACKGROUND
Binding of two 9-O-(ω-amino) alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U)(•)poly(A)(*)poly(U) was studied by various biophysical techniques.


RESULTS
Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5 °C compared to a 17.5 °C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain.


CONCLUSIONS
Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena.
Biophysical Chemistry Laboratory, Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Debipreeta
D
Bhowmik
Suman
S
Das
Maidul
M
Hossain
Lucy
L
Haq
Gopinatha
G
Suresh Kumar
D001599:Berberine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D055592:Biophysical Phenomena; D004583:Electrons; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D011061:Poly A / Q000737:chemistry* / Q000378:metabolism; D011072:Poly U / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics; D014783:Viscosity
D001599:Berberine; D011061:Poly A; D011072:Poly U; D012313:RNA