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Structure of a human telomeric DNA sequence stabilized by 8‐bromoguanosine substitutions, as determined by NMR in a K + solution
Author(s) -
Matsugami Akimasa,
Xu Yan,
Noguchi Yuuki,
Sugiyama Hiroshi,
Katahira Masato
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05881.x
Subject(s) - antiparallel (mathematics) , telomere , guanine , intramolecular force , g quadruplex , nucleic acid , chemistry , dna , stereochemistry , molecule , crystallography , sequence (biology) , nucleotide , biochemistry , physics , organic chemistry , quantum mechanics , magnetic field , gene
The structure of human telomeric DNA is controversial; it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K + is particularly interesting, but the structure is yet to be elucidated, due to possible conformational heterogeneity. Here, a unique strategy is applied to stabilize one such structure in a K + solution by substituting guanosines with 8‐bromoguanosines at proper positions. The resulting spectra are cleaner and led to determination of the structure at a high atomic resolution. This demonstrates that the application of 8‐bromoguanosine is a powerful tool to overcome the difficulty of nucleic acid structure determination arising from conformational heterogeneity. The obtained structure is a mixed‐parallel/antiparallel quadruplex. The structure of telomeric DNA was recently reported in another study, in which stabilization was brought about by mutation and resultant additional interactions [Luu KN, Phan AT, Kuryavyi V, Lacroix L & Patel DJ (2006) Structure of the human telomere in K + solution: an intramolecular (3+1) G‐quadruplex scaffold. J Am Chem Soc 128 , 9963–9970]. The structure of the guanine tracts was similar between the two. However, a difference was seen for loops connecting guanine tracts, which may play a role in the higher order arrangement of telomeres. Our structure can be utilized to design a small molecule which stabilizes the quadruplex. This type of molecule is supposed to inhibit a telomerase and thus is expected to be a candidate anticancer drug.