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Synlett
J. Mao, D. Bong
Letter
more efficient with bPNA. It is possible that alternative
side-chain designs could elevate the affinity of peptoids for
DNA. These, and further structural studies, are currently
under way.
Acknowledgment
This project was supported by the NSF.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380698.
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References and Notes
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Figure 2 Top: Thermal transitions of 1:1 DNA–peptoid complexes
monitored by UV absorbance at λ = 260 nm, with peptoids as indicated
and dT C T DNA at 2 μM concentration. (AbM) was complexed with
(7) Ma, M.; Bong, D. Org. Biomol. Chem. 2011, 9, 7296.
(8) Ma, M.; Bong, D. Langmuir 2011, 27, 1480.
6
4
6
8
dT C T . Bottom: Representative circular dichroism spectra showing
(9) Ma, M.; Paredes, A.; Bong, D. J. Am. Chem. Soc. 2008, 130, 14456.
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:1 peptoid–DNA complexation (20 μM each) of dT C T alone (---) and
6 4 6
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6
4
6
6
(
12) Kawasaki, T.; Tokuhiro, M.; Kimizuka, N.; Kunitake, T. J. Am.
3
8 °C.20 The origin of this difference is not clear. The 6mer
Chem. Soc. 2001, 123, 6792.
(
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13) Ariga, K.; Kunitake, T. Acc. Chem. Res. 1998, 31, 371.
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peptoid (AbM)6 is isomeric with 6mer bPNA (Figure 1).
Thus, the side chains were identical in both peptide and
peptoid, but simply placed on the amide nitrogen in the
peptoid rather than the α-carbon of the peptide. This pep-
toid–DNA complex is 19 °C lower in Tm than the isomeric
bPNA–DNA complex. While disappointing, this is also a cu-
rious finding. Given the identical length of the side chains,
the origin of the difference in DNA-binding affinity be-
tween peptide and peptoid isomers must derive from the
backbone itself. The peptoid backbone is less polar than the
peptide as a result of the tertiary amide linkages; the pep-
toid thus lacks amide NH hydrogen bond donors and only
has carbonyl–hydrogen bond acceptors. Additionally, the
peptide is composed of all L-amino acids, while the peptoid
lacks chiral centers. These physical characteristics lead to
conformational differences that could lead to decreased
2004, 33, 415.
(
15) Lange, R. F. M.; Beijer, F. H.; Sijbesma, R. P.; Hooft, R. W. W.;
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(
(
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18) Jahromi, A. H.; Nguyen, L.; Fu, Y.; Miller, K. A.; Baranger, A. M.;
Zimmerman, S. C. ACS Chem. Biol. 2013, 8, 1037.
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22) Xia, X.; Piao, X.; Bong, D. J. Am. Chem. Soc. 2014, 136, 7265.
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27,35,36
peptoid–DNA affinity.
ides in conventional PNA backbones does not lead to DNA
binding, and peptoid backbones have been previously
shown to display weaker DNA binding than peptides.32
Thus, despite the identical spacing of the triazine bases in
the peptoid and bPNA backbones, complexation is markedly
Indeed, backbone tertiary am-
(
(
24) Nielsen, P. E. Acc. Chem. Res. 1999, 32, 624.
25) Huang, Y.; Dey, S.; Zhang, X.; Sönnichsen, F.; Garner, P. J. Am.
Chem. Soc. 2004, 126, 4626.
27
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Natl. Acad. Sci. U.S.A. 1993, 90, 7518.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1581–1585