A new modified thrombin binding aptamer containing a 5′-5′ inversion of polarity site

The solution structure of a new modified thrombin binding aptamer (TBA) containing a 5′-5′ inversion of polarity site, namely d(3′GGT5′-5′TGGTGTGGTTGG3′), is reported. NMR and CD spectroscopy, as well as molecular dynamic and mechanic calculations, have been used to characterize the 3D structure. Th...

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Bibliographic Details
Published in:Nucleic acids research 2006-12, Vol.34 (22), p.6653-6662
Main Authors: Martino, Luigi, Virno, Ada, Randazzo, Antonio, Virgilio, Antonella, Esposito, Veronica, Giancola, Concetta, Bucci, Mariarosaria, Cirino, Giuseppe, Mayol, Luciano
Format: Article
Language:English
Subjects:
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - pharmacology
Humans
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Structural Biology
Structure-Activity Relationship
Thermodynamics
Thrombin - antagonists & inhibitors
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Summary:The solution structure of a new modified thrombin binding aptamer (TBA) containing a 5′-5′ inversion of polarity site, namely d(3′GGT5′-5′TGGTGTGGTTGG3′), is reported. NMR and CD spectroscopy, as well as molecular dynamic and mechanic calculations, have been used to characterize the 3D structure. The modified oligonucleotide is characterized by a chair-like structure consisting of two G-tetrads connected by three edge-wise TT, TGT and TT loops. d(3′GGT5′-5′TGGTGTGGTTGG3′) is characterized by an unusual folding, being three strands parallel to each other and only one strand oriented in opposite manner. This led to an anti-anti-anti-syn and syn-syn-syn-anti arrangement of the Gs in the two tetrads. The thermal stability of the modified oligonucleotide is 4°C higher than the corresponding unmodified TBA. d(3′GGT5′-5′TGGTGTGGTTGG3′) continues to display an anticoagulant activity, even if decreased with respect to the TBA.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkl915