Drug release by pH-responsive molecular tweezers : atomistic details from molecular modeling
Copyright © 2014 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 35(2014), 21 vom: 05. Aug., Seite 1545-51 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2014
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't density functional theory drug release drug targeting molecular switching molecular tweezers pH-responsive molecules steered molecular dynamics Pyridines |
| Zusammenfassung: | Copyright © 2014 Wiley Periodicals, Inc. pH-responsive molecular tweezers have been proposed as an approach for targeting drug-delivery to tumors, which tend to have a lower pH than normal cells. We performed a computational study of a pH-responsive molecular tweezer using ab initio quantum chemistry in the gas-phase and molecular dynamics (MD) simulations in solution. The binding free energy in solution was calculated using steered MD. We observe, in atomistic detail, the pH-induced conformational switch of the tweezer and the resulting release of the drug molecule. Even when the tweezer opens, the drug molecule remains near a hydrophobic arm of the molecular tweezer. Drug release cannot occur, it seems, unless the tweezer is in a hydrophobic environment with low pH |
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| Beschreibung: | Date Completed 23.04.2015 Date Revised 26.06.2014 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.23652 |