Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency |
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| Authors: | Maximilian C R Buff Florian Sch?fer Bernhard Wulffen Jens Müller Bernd P?tzsch Alexander Heckel Günter Mayer |
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| Institution: | 1.University of Frankfurt, Cluster of Excellence Macromolecular Complexes, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany, 2.Strathclyde Institute for Pharmacy and Biological Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, and Life and Medical Sciences, University of Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn and 3.Institute for Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany |
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| Abstract: | 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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