Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency

M.C.R. Buff, F. Schäfer, Bernhard Wulffen, Jens Müller, Bernd Pötzsch, A. Heckel, G. Mayer

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.
LanguageEnglish
Pages2111-2118
Number of pages7
JournalNucleic Acids Research
Volume38
Issue number6
DOIs
Publication statusPublished - Dec 2009

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Light
Anticoagulants
Clinical Trials
Proteins
thrombin aptamer

Keywords

  • aptamers
  • terminal extensions
  • light-regulation efficiency
  • nucleic acids

Cite this

Buff, M. C. R., Schäfer, F., Wulffen, B., Müller, J., Pötzsch, B., Heckel, A., & Mayer, G. (2009). Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency. Nucleic Acids Research, 38(6), 2111-2118. https://doi.org/10.1093/nar/gkp1148
Buff, M.C.R. ; Schäfer, F. ; Wulffen, Bernhard ; Müller, Jens ; Pötzsch, Bernd ; Heckel, A. ; Mayer, G. / Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency. In: Nucleic Acids Research. 2009 ; Vol. 38, No. 6. pp. 2111-2118.
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Buff, MCR, Schäfer, F, Wulffen, B, Müller, J, Pötzsch, B, Heckel, A & Mayer, G 2009, 'Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency' Nucleic Acids Research, vol. 38, no. 6, pp. 2111-2118. https://doi.org/10.1093/nar/gkp1148

Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency. / Buff, M.C.R.; Schäfer, F.; Wulffen, Bernhard; Müller, Jens; Pötzsch, Bernd; Heckel, A.; Mayer, G.

In: Nucleic Acids Research, Vol. 38, No. 6, 12.2009, p. 2111-2118.

Research output: Contribution to journalArticle

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AU - Schäfer, F.

AU - Wulffen, Bernhard

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AU - Heckel, A.

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