Study on effects of molecular crowding on G-quadruplex-ligand binding and ligand-mediated telomerase inhibition. Yaku, H., Murashima, T., Tateishi-Karimata, H., Nakano, S., Miyoshi, D., & Sugimoto, N. Methods (San Diego, Calif.), 64(1):19–27, April, 2013. Publisher: Elsevier Inc.![Study on effects of molecular crowding on G-quadruplex-ligand binding and ligand-mediated telomerase inhibition. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex The telomere G-quadruplex-binding and telomerase-inhibiting capacity of two cationic (TMPyP4 and PIPER) and two anionic (phthalocyanine and Hemin) G-quadruplex-ligands were examined under conditions of molecular crowding (MC). Osmotic experiments showed that binding of the anionic ligands, which bind to G-quadruplex DNA via π-π stacking interactions, caused some water molecules to be released from the G-quadruplex/ligand complex; in contrast, a substantial number of water molecules were taken up upon electrostatic binding of the cationic ligands to G-quadruplex DNA. These behaviors of water molecules maintained or reduced the binding affinity of the anionic and the cationic ligands, respectively, under MC conditions. Consequently, the anionic ligands (phthalocyanine and Hemin) robustly inhibited telomerase activity even with MC; in contrast, the inhibition of telomerase caused by cationic TMPyP4 was drastically reduced by MC. These results allow us to conclude that the binding of G-quadruplex-ligands to G-quadruplex via non-electrostatic interactions is preferable for telomerase inhibition under physiological conditions.
@article{Yaku2013,
title = {Study on effects of molecular crowding on {G}-quadruplex-ligand binding and ligand-mediated telomerase inhibition.},
volume = {64},
issn = {1095-9130},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23562626},
doi = {10.1016/j.ymeth.2013.03.028},
abstract = {The telomere G-quadruplex-binding and telomerase-inhibiting capacity of two cationic (TMPyP4 and PIPER) and two anionic (phthalocyanine and Hemin) G-quadruplex-ligands were examined under conditions of molecular crowding (MC). Osmotic experiments showed that binding of the anionic ligands, which bind to G-quadruplex DNA via π-π stacking interactions, caused some water molecules to be released from the G-quadruplex/ligand complex; in contrast, a substantial number of water molecules were taken up upon electrostatic binding of the cationic ligands to G-quadruplex DNA. These behaviors of water molecules maintained or reduced the binding affinity of the anionic and the cationic ligands, respectively, under MC conditions. Consequently, the anionic ligands (phthalocyanine and Hemin) robustly inhibited telomerase activity even with MC; in contrast, the inhibition of telomerase caused by cationic TMPyP4 was drastically reduced by MC. These results allow us to conclude that the binding of G-quadruplex-ligands to G-quadruplex via non-electrostatic interactions is preferable for telomerase inhibition under physiological conditions.},
number = {1},
journal = {Methods (San Diego, Calif.)},
author = {Yaku, Hidenobu and Murashima, Takashi and Tateishi-Karimata, Hisae and Nakano, Shu-Ichi and Miyoshi, Daisuke and Sugimoto, Naoki},
month = apr,
year = {2013},
pmid = {23562626},
note = {Publisher: Elsevier Inc.},
keywords = {\#nosource},
pages = {19--27},
}
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Osmotic experiments showed that binding of the anionic ligands, which bind to G-quadruplex DNA via π-π stacking interactions, caused some water molecules to be released from the G-quadruplex/ligand complex; in contrast, a substantial number of water molecules were taken up upon electrostatic binding of the cationic ligands to G-quadruplex DNA. These behaviors of water molecules maintained or reduced the binding affinity of the anionic and the cationic ligands, respectively, under MC conditions. Consequently, the anionic ligands (phthalocyanine and Hemin) robustly inhibited telomerase activity even with MC; in contrast, the inhibition of telomerase caused by cationic TMPyP4 was drastically reduced by MC. 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