Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution.

R F Macaya; P Schultze; F W Smith; J A Roe; J Feigon

doi:10.1073/pnas.90.8.3745

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Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution.

R F Macaya·P Schultze·F W Smith·J A Roe·J Feigon

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Abstract

We have used two-dimensional 1H NMR spectroscopy to study the conformation of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG) in solution. This is one of a series of thrombin-binding DNA aptamers with a consensus 15-base sequence that was recently isolated and shown to inhibit thrombin-catalyzed fibrin clot formation in vitro [Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H. & Toole, J. J. (1992) Nature (London) 355, 564-566]. The oligonucleotide forms a unimolecular DNA quadruplex consisting of two G-quartets connected by two TT loops and one TGT loop. A potential T.T bp is formed between the two TT loops across the diagonal of the top G-quartet. Thus, all of the invariant bases in the consensus sequence are base-paired. This aptamer structure was determined by NMR and illustrates that this molecule forms a specific folded structure. Knowledge of this structure may be used in the further development of oligonucleotide-based thrombin inhibitors.

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Base Sequence Binding Sites DNA Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Nucleic Acid Conformation Oligodeoxyribonucleotides Thrombin Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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R F Macaya, P Schultze, F W Smith, J A Roe, J Feigon. 1993-04-15. Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution.. https://doi.org/10.1073/pnas.90.8.3745

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