An interlocked dimeric parallel-stranded DNA quadruplex: a potent inhibitor of HIV-1 integrase. Phan, A. T., Kuryavyi, V., Ma, J., Faure, A., Andréola, M., & Patel, D. J Proceedings of the National Academy of Sciences of the United States of America, 102(3):634–9, January, 2005. ISBN: 0027-8424 (Print) 0027-8424 (Linking)![An interlocked dimeric parallel-stranded DNA quadruplex: a potent inhibitor of HIV-1 integrase. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex We report on the NMR-based solution structure of the 93del d(GGGGTGGGAGGAGGGT) aptamer, a potent nanomolar inhibitor of HIV-1 integrase. This guanine-rich DNA sequence adopts an unusually stable dimeric quadruplex architecture in K+ solution. Within each 16-nt monomer subunit, which contains one A.(G.G.G.G) pentad sandwiched between two G.G.G.G tetrads, all G-stretches are parallel, and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through mutual pairing of G1 of one monomer, with G2, G6, and G13 of the other monomer, to complete G.G.G.G tetrad formation. There are three single-nucleotide double-chain-reversal loops within each monomer fold, such that the first (T5) and third (A12) loops bridge three G-tetrad layers, whereas the second (A9) loop bridges two G-tetrad layers and participates in A.(G.G.G.G) pentad formation. Results of NMR and of integrase inhibition assays on loop-modified sequences allowed us to propose a strategy toward the potential design of improved HIV-1 integrase inhibitors. Finally, we propose a model, based on molecular docking approaches, for positioning the 93del dimeric DNA quadruplex within a basic channel/canyon formed between subunits of a dimer of dimers of HIV-1 integrase.
@article{Phan2005,
title = {An interlocked dimeric parallel-stranded {DNA} quadruplex: a potent inhibitor of {HIV}-1 integrase.},
volume = {102},
issn = {0027-8424},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15637158%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC545538 http://www.pnas.org/cgi/doi/10.1073/pnas.0406278102 http://www.ncbi.nlm.nih.gov/pubmed/15637158 http://www.pubmedcentral.nih.gov/articlerend},
doi = {10.1073/pnas.0406278102},
abstract = {We report on the NMR-based solution structure of the 93del d(GGGGTGGGAGGAGGGT) aptamer, a potent nanomolar inhibitor of HIV-1 integrase. This guanine-rich DNA sequence adopts an unusually stable dimeric quadruplex architecture in K+ solution. Within each 16-nt monomer subunit, which contains one A.(G.G.G.G) pentad sandwiched between two G.G.G.G tetrads, all G-stretches are parallel, and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through mutual pairing of G1 of one monomer, with G2, G6, and G13 of the other monomer, to complete G.G.G.G tetrad formation. There are three single-nucleotide double-chain-reversal loops within each monomer fold, such that the first (T5) and third (A12) loops bridge three G-tetrad layers, whereas the second (A9) loop bridges two G-tetrad layers and participates in A.(G.G.G.G) pentad formation. Results of NMR and of integrase inhibition assays on loop-modified sequences allowed us to propose a strategy toward the potential design of improved HIV-1 integrase inhibitors. Finally, we propose a model, based on molecular docking approaches, for positioning the 93del dimeric DNA quadruplex within a basic channel/canyon formed between subunits of a dimer of dimers of HIV-1 integrase.},
number = {3},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
author = {Phan, Anh Tuân and Kuryavyi, Vitaly and Ma, Jin-Biao and Faure, Aurélie and Andréola, Marie-Line and Patel, Dinshaw J},
month = jan,
year = {2005},
pmid = {15637158},
note = {ISBN: 0027-8424 (Print) 0027-8424 (Linking)},
keywords = {\#nosource},
pages = {634--9},
}
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