Spectroscopic and Thermodynamic Studies on the Binding of Sanguinarine and Berberine to Triple and Double Helical DNA and RNA Structures

Abstract

A comparative study on the interaction of sanguinarine and berberine with DNA and RNA triplexes and their parent duplexes was performed, by using a combination of spectrophotometric, UV thermal melting, circular dichroic and thermodynamic techniques. Formation of the DNA and RNA triplexes was confirmed from UV-melting and circular dichroic measurements. The interaction process was characterized by increase of thermal melting temperature, perturbation in circular dichroic spectrum and the typical hypochromic and bathochromic effects in the absorption spectrum. Scatchard analysis indicated that both the alkaloids bound to the triplex and duplex structures in a non-cooperative manner and the binding was stronger to triplexes than to parent duplexes. Thermal melting studies further indicated that sanguinarine stabilized the Hoogsteen base paired third strand of both DNA and RNA triplexes more tightly compared to their Watson-Crick strands, while berberine stabilized the third strand only without affecting the Watson-Crick strand. However, sanguinarine stabilized the parent duplexes while no stabilization was observed with berberine under identical conditions. Circular dichroic studies were also consistent with the observation that perturbations of DNA and RNA triplexes were more compared to their parent duplexes in presence of the alkaloids. Thermodynamic data revealed that binding of sanguinarine and berberine to triplexes (T.AxT and U.AxU) and duplexes (A.T and A.U) showed negative enthalpy changes and positive entropy changes but that of sanguinarine to C.GxC(+) triplex and G.C duplex exhibited negative enthalpy and negative entropy changes. Taken together, these results suggest that both sanguinarine and berberine can bind and stabilize the DNA and RNA triplexes more strongly than their respective parent duplexes.

Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives

“…[183][184][185][186] These include tethering of intercalating agents to triplex forming oligionucleotides, photoinduction of covalent cross-links between the third strand and the under lying duplex via a photoactivating agent, use of oligonucleotide analogs with modified bases or intercalating agent that can selectively stabilize the triplexes. Several intercalating ligands 183,[187][188][189][190] are reported to intercalate between the nuclobases of DNA triplexes and improve both stability and sequence specificity of the Hoogsteen base paired third strand. Ren and Chaires 187 have first demonstrated that berberine preferentially and very strongly bound to poly(dT).poly(dA)xpoly(dT) triplex compared to the poly(dA).poly(dT) duplex from novel competition dialysis and thermal melting experiments.…”

Protoberberine Alkaloids Berberine, Palmatine, and Coralyne Binding to Poly(dT)⋅(Poly(dA)⋅Poly(dT)) Triplex: Comparative Structural Aspects and Energetics Profiles of the Interaction

“…In the present study we report for the first time that all the three alkaloids bind the triplex structure in a cooperative manner. Previous studies on coralyneÀDNA triplex suggested non-cooperative binding [23] [42] [43]. It is likely that the cooperativity phenomenon observed here was missed in previous studies due to the absence of binding data below an r value of 0.2.…”

“…Conformational changes of the triplex on binding to the alkaloids were investigated from intrinsic CD studies. The intrinsic CD spectra of the T · AT triplex was characterized by a positive band in the region of 275 -285 nm, followed by a hump in the 260 -270-nm region, followed by a large negative band around 245 nm and a bell shaped band in the negative side in the region of 220 -235 nm [23]. The conformation of the triplex was found to be perturbed in presence of all the three alkaloids (Fig.…”

“…1) constitute an important group of alkaloids known for several years for their biological applications including potential anticancer properties [30 -32]. DNA and RNA have been thought to be the biological targets of these compounds in manifesting their anticancer activities, and, accordingly, the binding properties of these alkaloids have been described in many recent publications on the binding to poly(A), triplexes, and quadruplexes [23] [33 -38]. Particularly noteworthy was the strong binding of berberine and coralyne to poly(A) with affinity in the order close to 10 6 m À 1…”

Electrochemistry of Benzophenanthridine Alkaloids. Formation and Characterization of Redox Active Films from Products of Sanguinarine and Chelerythrine Oxidation

“…They represent small (15 derivatives known) yet intensely studied group of natural products because of their numerous biochemical as well as medical implications e.g. antimicrobial [1], antiinflamatory [2] and antifungal [3] activities, interactions with DNA [4], inhibition of reverse transcriptase [5], inhibition of oxidative burst via affecting NADPH oxidase activity [6] etc. The most common naturally occurring benzophenanthridine alkaloids are sanguinarine and chelerythrine.…”