Communication
ChemComm
10 K. G. Smith, J. Jie, G. E. Fox and X. Gao, Nucleic Acids Res., 1995, 23,
4303–4311.
11 A. A. Figueroa and S. Delaney, J. Biol. Chem., 2010, 285, 14648–14657.
12 C. Chang, C. R. Jhan and M. H. Hou, Curr. Top. Med. Chem., 2015,
15, 1398–1408.
13 A. Granzhan, N. Kotera and M. P. Teulade-Fichou, Chem. Soc. Rev.,
2014, 43, 3630–3665.
14 B. M. Zeglis, V. C. Pierre and J. K. Barton, Chem. Commun., 2007, 4565–4579.
15 K. Nakatani, Bull. Chem. Soc. Jpn., 2009, 82, 1055–1069.
16 K. Nakatani, S. Hagihara, Y. Goto, A. Kobori, M. Hagihara,
G. Hayashi, M. Kyo, M. Nomura, M. Mishima and C. Kojima, Nat.
Chem. Biol., 2005, 1, 39–43.
Fig. 5 One of the possible binding complexes between p-NCTB and two
ODN helices (A and B) containing a dCGGG/dCGGG sequence. Two
p-NCTB molecules are shown in red and magenta. The dCGGG/dCGGG
sequence contains two overlapped dCGG/dGGG sites as depicted in blue
rectangles, each of which can be recognized by NCD moieties. Interhelical
G–C interactions shown by dotted arrows might stabilize the complexes.
17 (a) C. Dohno and K. Nakatani, Chem. Soc. Rev., 2011, 40, 5718–5729;
(b) C. Dohno, I. Kohyama, M. Kimura, M. Hagihara and K. Nakatani,
Angew. Chem., Int. Ed., 2013, 52, 9976–9979; (c) C. Dohno, M. Kimura
and K. Nakatani, Angew. Chem., Int. Ed., 2018, 57, 506–510.
18 S. Amrane, A. De Cian, F. Rosu, M. Kaiser, E. De Pauw, M. P. Teulade-
Fichou and J. L. Mergny, ChemBioChem, 2008, 9, 1229–1234.
19 (a) A. J. Angelbello, J. L. Chen and M. D. Disney, Ann. N. Y. Acad. Sci.,
2019, 1–15; (b) A. Pushechnikov, M. M. Lee, J. L. Childs-Disney,
K. Sobczak, J. M. French, C. A. Thornton and M. D. Disney, J. Am.
Chem. Soc., 2009, 131, 9767–9779; (c) M. D. Disney, B. Liu, W. Yang,
C. Sellier, T. Tran, N. Charlet-berguerand and J. L. Childs-Disney,
ACS Chem. Biol., 2012, 7, 1711–1718; (d) Z. Su, Y. Zhang,
T. F. Gendron, P. O. Bauer, J. Chew, W. Y. Yang, E. Fostvedt,
K. Jansen-West, V. V. Belzil, P. Desaro, A. Johnston, K. Overstreet,
S. Y. Oh, P. K. Todd, J. D. Berry, M. E. Cudkowicz, B. F. Boeve,
D. Dickson, M. K. Floeter, B. J. Traynor, C. Morelli, A. Ratti, V. Silani,
R. Rademakers, R. H. Brown, J. D. Rothstein, K. B. Boylan,
L. Petrucelli and M. D. Disney, Neuron, 2014, 83, 1043–1050.
20 P. C. Gareiss, K. Sobczak, B. R. McNaughton, P. B. Palde, C. A. Thornton
and B. L. Miller, J. Am. Chem. Soc., 2008, 130, 16254–16261.
21 J. F. Arambula, S. R. Ramisetty, A. M. Baranger and S. C. Zimmerman,
Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 16068–16073.
22 (a) T. Peng, T. Murase, Y. Goto, A. Kobori and K. Nakatani, Bioorg. Med.
Chem. Lett., 2005, 15, 259–262; (b) T. Peng and K. Nakatani, Angew.
Chem., Int. Ed., 2005, 44, 7280–7283; (c) M. Hagihara, H. He, M. Kimura
and K. Nakatani, Bioorg. Med. Chem. Lett., 2012, 22, 2000–2003.
23 C. Dohno, I. Kohyama, C. Hong and K. Nakatani, Nucleic Acids Res.,
2012, 40, 2771–2781.
24 (a) R. J. Hagerman and P. Hagerman, Nat. Publ. Gr., 2016, 12, 403–412;
(b) Y. Fu, D. P. A. Kuhl, A. Piuuti, M. Pieretti, J. S. Sutcliffe, S. Richards,
J. J. A. Holden, R. G. Fenwick, S. T. Warren, B. A. Oostra, D. L. Nelson
and C. T. Caskey, Cell, 1991, 67, 1047–1056.
moieties to the dCGG/dGGG sites induces flipping out of C and
ꢀ
ꢀ
G at the 50 termini, assuming the similar binding mode to the
dCGG/dCGG–NCD.22 Hydrogen bonding interactions between the
extra helical bases might contribute to further stabilization of
the complex (simulated structures in Fig. S16, ESI†).38
ꢀ
ꢀ
In summary, we have developed a novel naphthyridine tetramer,
p-NCTB, for the selective recognition of tandem G–G mismatches.
The rigid and extended p-biphenyl linker contributed to the selective
binding of p-NCTB to dCGGG/dCGGG over dCGG/dCGG mis-
matches. We demonstrated that p-NCTB recognized two distal
dCGGG/dCGGG sites resulting in the formation of inter- and
intrastrand complexes depending on the sequence context. The
intrastrand binding (II) is more favorable than the interstrand
binding (I) as shown by higher binding affinity and thermal stability
of the complex. The favored intrastrand binding (II) of p-NCTB is
useful for targeting DNA sequences containing multiple dCGGG/
dCGGG sites, like the GGGGCC repeat responsible for ALS/FTD.25,26
Our study broadens the applications of synthetic ligands targeting
G–G mismatches, and the concept will be applicable in ligand
design targeting other mismatch-containing DNA/RNA sequences.
This work was supported by Grants in Aid for Scientific
Research (B) (18H02107) to C. D. and Specially Promoted Research
(26000007) to K. N. from the Japan Society for the Promotion of
Science ( JSPS).
25 M. DeJesus-Hernandez and I. R. Mackenzie, et al., Neuron, 2011, 72, 245–256.
26 (a) A. R. Haeusler, C. J. Donnelly and J. D. Rothstein, Nat. Rev.
Neurosci., 2016, 17, 383–395; (b) R. Balendra and A. M. Isaacs, Nat.
Rev. Neurol., 2018, 14, 544–558.
27 A. R. Haeusler, C. J. Donnelly, G. Periz, E. A. J. Simko, P. G. Shaw,
M. S. Kim, N. J. Maragakis, J. C. Troncoso, A. Pandey, R. Sattler,
J. D. Rothstein and J. Wang, Nature, 2014, 507, 195–200.
ˇ´
28 (a) J. Brcic and J. Plavec, Nucleic Acids Res., 2015, 43, 8590–8600; (b) J. Brcic
Conflicts of interest
and J. Plavec, Biochim. Biophys. Acta, Gen. Subj., 2017, 1861, 1237–1245.
29 (a) C. E. Pearson and R. R. Sinden, Curr. Opin. Struct. Biol., 1998, 8,
321–330; (b) B. Zamiri, M. Mirceta, K. Bomsztyk, R. B. Macgregor
and E. Pearson, Nucleic Acids Res., 2015, 43, 10055–10064.
30 M. Mitas, A. Yu, J. Dill and I. S. Haworth, Biochemistry, 1995, 34,
12803–12811.
There are no conflicts to declare.
Notes and references
31 Y. Zhang, C. Roland and C. Sagui, ACS Chem. Neurosci., 2017, 8,
578–591.
32 M. L. Bochman, K. Paeschke and V. A. Zakian, Nat. Rev. Genet., 2012,
13, 770–780.
1 G. M. Li, Cell Res., 2008, 18, 85–98.
2 R. R. Iyer, A. Pluciennik, V. Burdett and P. L. Modrich, Chem. Rev.,
2006, 106, 302–323.
3 R. R. Iyer, A. Pluciennik, M. Napierala and R. D. Wells, Annu. Rev.
Biochem., 2015, 84, 199–226.
4 M. H. M. Schmidt and C. E. Pearson, DNA Repair, 2016, 38, 117–126.
5 D. Bikard, C. Loot, Z. Baharoglu and D. Mazel, Microbiol. Mol. Biol.
Rev., 2010, 74, 570–588.
¨
33 R. Hansel-Hertsch, M. Di Antonio and S. Balasubramanian, Nat. Rev.
Mol. Cell Biol., 2017, 18, 279–284.
34 A. Yafe, S. Etzioni, P. Weisman-Shomer and M. Fry, Nucleic Acids
Res., 2005, 33, 2887–2900.
35 C. Hong, M. Hagihara and K. Nakatani, Angew. Chem., Int. Ed., 2011,
50, 4390–4393.
36 J. N. Weiss, FASEB J., 1997, 11, 835–841.
6 D. M. J. Lilley, Nucleic Acids Res., 1985, 13, 1443–1465.
7 C. T. McMurray, Nat. Rev. Genet., 2010, 11, 786–799.
8 S. M. Mirkin, Nature, 2007, 447, 932–940.
37 R. G. Cotton, N. R. Rodrigues and R. D. Campbell, Proc. Natl. Acad.
Sci. U. S. A., 1988, 85, 4397–4401.
38 S. Mukherjee, L. Błaszczyk, W. Rypniewski, C. Falschlunger,
R. Micura, A. Murata, C. Dohno, K. Nakatani and A. Kiliszek, Nucleic
Acids Res., 2019, 47, 10906–10913.
9 (a) C. E. Pearson and R. R. Sinden, Biochemistry, 1996, 35, 5041–5053;
(b) C. E. Pearson, A. Ewel, S. Acharya, R. A. Fishel and R. R. Sinden,
Hum. Mol. Genet., 1997, 6, 1117–1123; (c) C. E. Pearson, M. Tam,
Y. H. Wang, S. E. Montgomery, A. C. Dar, J. D. Cleary and K. Nichol,
Nucleic Acids Res., 2002, 30, 4534–4547.
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2019