Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Creator |
Agarwal, T
Roy, S Chakraborty, TK Maiti, S |
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| Subject |
Biochemistry & Molecular Biology
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| Description |
Quadruplex-specific molecules can serve as suitable drugs in cancer therapy. We have synthesized a pair of furan-based cyclic homooligopeptides, ligand 1 and ligand 2, to specifically target G-quadruplexes. We have shown by CD spectroscopy and UV melting that these ligands can effectively induce G-quadruplex structures in the G-rich 22-mer c-MYC DNA sequence and further stabilize the structure. Equilibrium binding constants measured by isothermal titration calorimeter methods indicate a high affinity of the ligands for the quadruplex structures (K similar to 10(7) M(-1)) and no affinity for the duplex DNA, demonstrating that these ligands are selective for G-quadruplex structures. Surface plasmon resonance was also used to compute the binding while fluorescence resonance energy transfer-based assay was additionally used to confirm the selectivity. Moreover, using real time PCR we observed up to 90% downregulation of c-MYC transcripts after 24 h of ligand treatment in HeLa cells. Using a luciferase assay we show the downregulation of the protein levels. Fluorescent-assisted cell sorter-based cell cycle analysis showed a prominent arrest of cells in the sub-G1 stage upon treatment of ligands that leads toward apoptosis. Altogether, these experiments support the hypothesis that the present molecules are effective in specifically binding and stabilizing quadruplexes and provide a suitable scaffold to develop into a quadruplex-targeting therapeutic agent.
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| Publisher |
AMER CHEMICAL SOCWASHINGTON1155 16TH ST, NW, WASHINGTON, DC 20036 USA
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| Date |
2011-09-20T12:07:05Z
2011-09-20T12:07:05Z 2010 |
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| Type |
Article
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| Identifier |
BIOCHEMISTRY
0006-2960 http://hdl.handle.net/123456789/13098 |
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| Language |
English
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