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Sensing of Different Human Telomeric G-Quadruplex DNA Topologies by Natural Alkaloid Allocryptopine Using Spectroscopic Techniques.

A new interesting article has been published in J Phys Chem B. 2018 Oct 22. doi: 10.1021/acs.jpcb.8b07856. [Epub ahead of print] and titled:

Sensing of Different Human Telomeric G-Quadruplex DNA Topologies by Natural Alkaloid Allocryptopine Using Spectroscopic Techniques.

Authors of this article are:

Mandal P, Sahoo D, Saha S, Chowdhury J.

A summary of the article is shown below:

Current article describes how does a natural alkaloid Allocryptopine (ALL) able to differentiate two forms of biologically relevant human telomeric (htel22) G-quadruplex DNAs (GQ-DNA) depending upon the presence of K+ and Na+ ions by steady state and time-resolved spectroscopic techniques. For both interactions predominant involvements of static type quenching mechanism with the negligible influence of dynamic collision are established by UV-Vis absorption and fluorescence emission study which is further supported by fluorescence lifetime measurements. ALL exhibits appreciable affinity towards both GQ-DNAs. Both the mixed-hybrid (3+1) quadruplex structures in K+ ions, and basket-type anti-parallel quadruplex structure in Na+ condition are converted to parallel types in the presence of ALL. FID experiment revealed modest selectivity of ALL to the both quadruplexes over duplex DNA along with higher selectivity for anti-parallel types among the two quadruplexes via groove and/or loop binding, which is distinct from the conventional -staking of the ligands on external G-quartets. ALL stabilized both GQ-DNA topologies moderately. The differences in the dynamics of ALL within both DNA environments have been demonstrated vividly by the time-resolved anisotropy measurements using wobbling-in-cone model. These results suggest groove binding with anti-parallel G-quartet with high affinity and moderate loop binding with mixed hybrid G-quartet accompanied by the partial end-staking additionally in both the cases. Our conclusions are further supported by steady state anisotropy measurements and molecular docking. Present investigation could be used in the development of biocompatible anti tumour/anti cancer agent targeting particular GQ-DNA conformation.

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