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PMID: 8475124 Published · ppublish English 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.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 8 ·1993-04-15 ·Pages 3745-9

Macaya RF, Schultze P, Smith FW, Roe JA, Feigon J

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.

MeSH Terms
Base Sequence Binding Sites DNA/chemistry,metabolism Magnetic Resonance Spectroscopy/methods Models, Molecular Molecular Sequence Data Nucleic Acid Conformation Oligodeoxyribonucleotides/chemical synthesis,chemistry,metabolism Thrombin/chemistry,metabolism
Chemicals
Oligodeoxyribonucleotides DNA Thrombin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Macaya R F
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
Schultze P
Smith F W
Roe J A
Feigon J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.8.3745
Published
1993-04-15
Pages
3745-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46378
Subset
IM
Grants
NIGMS NIH HHS · R01 GM 37254-06 · United States
NIGMS NIH HHS · R01 GM48123-01 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.8.3745 PMC Full Text View journal details
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