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.
Buff
Maximilian C R
MC
University of Frankfurt, Cluster of Excellence Macromolecular Complexes, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Schäfer
Florian
F
Wulffen
Bernhard
B
Müller
Jens
J
Pötzsch
Bernd
B
Heckel
Alexander
A
Mayer
Günter
G
D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D002942:Circular Dichroism; D008027:Light
D000925:Anticoagulants; D052157:Aptamers, Nucleotide; C081676:thrombin aptamer