FEBS Letters
Volume 582, Issue 13 , Pages 1835-1839, 11 June 2008

Imino proton exchange rates imply an induced-fit binding mechanism for the VEGF165-targeting aptamer, Macugen

Edited by Hans Eklund

  • Joon-Hwa Lee

      Affiliations

    • Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309-0215, USA
    • Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea
    • ,
  • Fiona Jucker

      Affiliations

    • Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309-0215, USA
    • ,
  • Arthur Pardi

      Affiliations

    • Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309-0215, USA
    • Corresponding Author InformationCorresponding author. Fax: +1 303 492 2439.

Received 22 March 2008; received in revised form 26 April 2008; accepted 4 May 2008. published online 14 May 2008.

Abstract 

The 2′-fluoro/2′-O-methyl modified RNA aptamer Macugen is a potent inhibitor of the angiogenic regulatory protein, VEGF165. Macugen binds with high affinity to the heparin-binding domain (HBD) of VEGF165. Hydrogen exchange rates of the imino protons were measured for free Macugen and Macugen bound to the HBD or full-length VEGF to better understand the mechanism for high affinity binding. The results here show that the internal loop and hairpin loop of Macugen are highly dynamic in the free state and are greatly stabilized and/or protected from solvent upon protein binding.

Keywords: NMR, Hydrogen exchange rate, RNA aptamer, VEGF, RNA–protein complex

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PII: S0014-5793(08)00384-0

doi:10.1016/j.febslet.2008.05.003

FEBS Letters
Volume 582, Issue 13 , Pages 1835-1839, 11 June 2008

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