title: Interaction of 9-O-N-aryl/arylalkyl amino carbonyl methyl berberine analogs with single stranded ribonucleotides.
abstract: Studies on the molecular aspects of alkaloid-RNA complexation are of prime importance for the development of rational RNA targeted drug design strategies. Towards this goal, the binding aspects of three novel 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberine analogs to four single stranded ribonucleotides, poly(G), poly(I), poly(C) and poly(U), were studied for the first time employing multifaceted biophysical tools. Absorbance and fluorescence studies revealed that these analogs bound non-cooperatively to poly(G) and poly(I) with binding affinities remarkably higher than berberine. The binding of these analogs to poly(U) and poly(C) was weaker in comparison to poly(G) and poly(I) but were one order higher in comparison to berberine. Quantum efficiency values revealed that energy transfer occurred from the RNA bases to the analogs upon complexation. The binding was dominated by large positive entropic contributions and small but favorable enthalpic contributions. Salt dependent studies established that the binding was dominated by hydrophobic forces that contributed around 90% of the total standard molar Gibbs energy. The chain length of the substitution at the 9-position was found to be critical in modulating the binding affinities. These results provide new insights into the binding efficacy of these novel berberine analogs to single stranded RNA sequences.
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India; Biophysical Chemistry Laboratory, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
authors.forename: Parasuraman
authors.initials: P
authors.lastname: Jaisankar
authors.affiliation: Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India; Biophysical Chemistry Laboratory, 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* / Q000378:metabolism; D001665:Binding Sites; D002151:Calorimetry; D002942:Circular Dichroism; D009690:Nucleic Acid Conformation; D009994:Osmolar Concentration; D011066:Poly C / Q000737:chemistry / Q000378:metabolism; D011068:Poly G / Q000737:chemistry / Q000378:metabolism; D011069:Poly I / Q000737:chemistry / Q000378:metabolism; D011072:Poly U / Q000737:chemistry / Q000378:metabolism; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012265:Ribonucleotides / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics
chemical_list: D012265:Ribonucleotides; D001599:Berberine; D011068:Poly G; D011069:Poly I; D011072:Poly U; D011066:Poly C; D012313:RNA
keywords: 9-O-N-aryl/arylalkyl amino carbonyl methyl substituted berberines; Energetics; Intercalation; Single stranded RNA binding