Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency
Aptamers that can be regulated with light allow precise control of protein activity in space and time and hence of biological function in general. In a previous study, we showed that the activity of the thrombin-binding aptamer HD1 can be turned off by irradiation using a light activatable "caged" intramolecular antisense-domain. However, the activity of the presented aptamer in its ON state was only mediocre. Here we studied the nature of this loss in activity in detail and found that switching from 5'- to 3'-extensions affords aptamers that are even more potent than the unmodified HD1. In particular we arrived at derivatives that are now more active than the aptamer NU172 that is currently in phase 2 clinical trials as an anticoagulant. As a result, we present light-regulatable aptamers with a superior activity in their ON state and an almost digital ON/OFF behavior upon irradiation.
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| Author: | Maximilian Buff, Florian Schäfer, Bernhard Wulffen, Jens Müller, Bernd Pötzsch, Alexander Heckel, Günter Mayer |
|---|---|
| URN: | urn:nbn:de:hebis:30-85087 |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 12.11.2010 |
| Year of first Publication: | 2009 |
| Publishing Institution: | Univ.-Bibliothek Frankfurt am Main |
| Source: | Nucleic Acids Research, vol. 38, no. 6, S. 2111-2118 ; doi: 10.1093/nar/gkp1148 ; First published online: December 8, 2009 |
| HeBIS PPN: | 230020453 |
| Institutes: | Biochemie und Chemie |
| Dewey Decimal Classification: | 570 Biowissenschaften; Biologie |
| Sammlungen: | Universitätspublikationen |
| Sondersammelgebiets-Volltexte Biologie | |
| Note: | © The Author(s) 2009. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Licence (German): |  Veröffentlichungsvertrag für Publikationen ohne Print on Demand |
