Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Giri, Prabal; Hossain, Maidul; Kumar, Gopinatha Suresh

doi:10.1016/j.ijbiomac.2006.03.026

Cited by 57 publications

(38 citation statements)

References 54 publications

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“…Small molecules, such as protoberberine alkaloids berberine, (48) palmatine, (49) coralyne (50) have been shown to bind strongly to single stranded poly(rA). The binding mode for these ligands is hypothesized to be a partial intercalation in which the ligand molecule is inserted between neighboring adenine bases through the stacking of the ligand between the bases on the chain (48).…”

Section: Resultsmentioning

confidence: 99%

Thermodynamics of Nucleic Acid “Shape Readout” by an Aminosugar

Davis

Ranjan

et al. 2011

Biochemistry

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Recognition of nucleic acids is important for our understanding of nucleic acid structure as well as for our understanding of nucleic acid-protein interactions. In addition to the direct readout mechanisms of nucleic acids such as H-bonding, shape recognition of nucleic acids is being increasingly recognized to play an equally important role in DNA recognition. Competition Dialysis, UV, Flourescent Intercalator displacement (FID), Computational Docking, and calorimetry studies were conducted to study the interaction of neomycin with a variety of nucleic acid conformations (shapes). At pH 5.5, these results suggest: (1) Neomycin binds three RNA structures (16S A site rRNA, poly(rA)•poly(rA), and poly(rA)•poly(rU)) with high affinities, Ka~107M−1. (2) The binding of neomycin to A-form GC-rich oligomer d(A2G15C15T2)2 has comparable affinity to RNA structures. (3) The binding of neomycin to DNA•RNA hybrids shows a three-fold variance attributable to their structural differences (poly(dA) •poly(rU), Ka=9.4×106M−1 and poly(rA)•poly(dT), Ka=3.1×106M−1). (4) The interaction of neomycin with DNA triplex poly(dA)•2poly(dT) yields a binding affinity of Ka=2.4×105M−1. (5) Poly(dA-dT)2 showed the lowest association constant for all nucleic acids studied (Ka=<105). (6) Neomycin binds to G-quadruplexes with Ka~104-105M−1. (7) Computational studies show that the decrease in major groove width in the B to A transition correlates with increasing neomycin affinity. Neomycin’s affinity for various nucleic acid structures can be ranked as follows, RNAs and GC-rich d(A2G15C15T2)2 structures > poly(dA)•poly(rU) > poly(rA)•poly(dT) > T•A-T triplex , G-quadruplexes, B-form AT-rich or GC-rich DNA sequences. The results illustrate the first example of a small molecule based ‘shape readout’ of different nucleic acid conformations.

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Section: Resultsmentioning

confidence: 99%

Thermodynamics of Nucleic Acid “Shape Readout” by an Aminosugar

Davis

Ranjan

et al. 2011

Biochemistry

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“…Small molecules that could bind strongly to single-stranded poly(A) may be useful as potential leads for controlling the mRNA-poly(A) chain elongation and in turn mRNA degradation as well as the conversion of single-stranded poly(A) to double stranded poly(A) that may open up an opportunity for modulating nucleic acid structure-functions. The plant alkaloids berberine and palmatine exhibit stronger binding to single stranded poly(A), but do not induce any self-structure formation in poly(A) helix [109, 114]. Binding of coralyne to the poly(A) helix leading to self structure formation was further supported by Giri and Kumar [79] and the binding process was found to be predominantly exothermic and enthalpy-driven with a stoichiometry of one coralyne per four adenines bases.…”

Section: Nucleic Acid Binding Aspects Of Bioactive Isoquinoline Almentioning

confidence: 99%

Polymorphic Nucleic Acid Binding of Bioactive Isoquinoline Alkaloids and Their Role in Cancer

Maiti

Kumar

2009

Journal of Nucleic Acids

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Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form) and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity.

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“…Some RNA binding molecules like aminoglycosides have been investigated, but due to the high toxicity, their usage in RNA therapeutics is limited [22]. Our laboratory has studied the interaction of a number of natural alkaloid molecules and has provided new data on the mode, mechanism and energetics of their interaction with single and ds RNAs [23][24][25][26][27][28]. Poly(A) has been the focus of increasing attention for its importance in mRNA functioning [29,30].…”

Section: Introductionmentioning

confidence: 99%