DOI: 10.1126/science.1088334. A Four-Base Paired Genetic Helix with Expanded Size

A Four-Base Paired Genetic Helix with Expanded Size

10.1126/science.1088334

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

We describe a new molecular class of genetic-pairing system that has a native DNA backbone but has all four base pairs replaced by new, larger pairs. The base pairs include size-expanded analogs of thymine and of adenine, both extended by the width of a benzene ring (2.4 Å). The expanded-diameter double helices are more thermodynamically stable than the Watson-Crick helix, likely because of enhanced base stacking. Structural data confirm a right-handed, double-stranded, and base-paired helical form. Because of the larger base size, all the pairs of this helical system are fluorescent, which suggests practical applications in detection of natural DNA and RNA. Our findings establish that there is no apparent structural or thermodynamic prohibition against genetic systems having sizes different from the natural one.

Bibliography

Liu, H., Gao, J., Lynch, S. R., Saito, Y. D., Maynard, L., & Kool, E. T. (2003). A Four-Base Paired Genetic Helix with Expanded Size. Science, 302(5646), 868â871.

Authors 6

Haibo Liu (first)
Jianmin Gao (additional)
Stephen R. Lynch (additional)
Y. David Saito (additional)
Lystranne Maynard (additional)
Eric T. Kool (additional)

References 28 Referenced 207

A. Murakami, K. R. Blake, P. S. Miller, Biochemistry24, 4041 (1985). (10.1021/bi00336a036) / Biochemistry (1985)
M. Matsukura et al., Proc. Natl. Acad. Sci. U.S.A.847706 (1987). (10.1073/pnas.84.21.7706) / Proc. Natl. Acad. Sci. U.S.A. (1987)
M. Egholm et al., Nature365, 566 (1993). (10.1038/365566a0) / Nature (1993)
10.1126/science.284.5423.2118
A. A. Koshkin et al., Tetrahedron54, 3607 (1998). (10.1016/S0040-4020(98)00094-5) / Tetrahedron (1998)
H. P. Rappaport, Nucleic Acids Res.16, 7253 (1988). (10.1093/nar/16.15.7253) / Nucleic Acids Res. (1988)
S. A. Benner et al., Pure Appl. Chem.70, 263 (1998). (10.1351/pac199870020263) / Pure Appl. Chem. (1998)
T. J. Matray, E. T. Kool, J. Am. Chem. Soc.120, 6191 (1998). (10.1021/ja9803310) / J. Am. Chem. Soc. (1998)
D. L. McMinn et al., J. Am. Chem. Soc.121, 11585 (1999). (10.1021/ja9925150) / J. Am. Chem. Soc. (1999)
T. Mitsui et al., J. Am. Chem. Soc.125, 5298 (2003). (10.1021/ja028806h) / J. Am. Chem. Soc. (2003)
10.1126/science.1080587
R. A. Lessor, K. J. Gibson, N. J. Leonard, Biochemistry23, 3868 (1984). (10.1021/bi00312a012) / Biochemistry (1984)
N. J. Leonard, M. A. Sprecker, A. G. Morrice, J. Am. Chem. Soc.98, 3987 (1976). (10.1021/ja00429a040) / J. Am. Chem. Soc. (1976)
J. Michel, J. J. Toulme, J. Vercauteren, S. Moreau, Nucleic Acids Res.24, 1127 (1996). (10.1093/nar/24.6.1127) / Nucleic Acids Res. (1996)
M. Hoffer, Chem. Ber.93, 2777 (1960). (10.1002/cber.19600931204) / Chem. Ber. (1960)
Details of nucleoside phosphoramidite synthesis and characterization of oligonucleotide synthesis and of thermodynamics methods are given in the Supporting Online Material.
H. Liu J. Gao E. T. Kool unpublished observations.
Hyperchromicity values of helices involving the expanded bases should not be directly compared with those of natural DNAs because the photophysical properties of xT and xA are different from those of T and A.
G. Prakash, E. T. Kool, J. Am. Chem. Soc.114, 3523 (1992). (10.1021/ja00035a056) / J. Am. Chem. Soc. (1992)
Thermal denaturation of the two single-stranded components alone under these conditions (5.0 μM in oligonucleotide) revealed transition temperatures of 26.5 and 27.5°C significantly lower than that of the duplex.
F. Seela, A. Melenewski, C. Wei, Bioorg. Med. Chem. Lett.17, 2173 (1997). / Bioorg. Med. Chem. Lett. (1997)
K. Groebke et al., Helv. Chim. Acta81, 375 (1998). (10.1002/hlca.19980810302) / Helv. Chim. Acta (1998)
M. F. H. Hoffmann, A. M. Brückner, T. Hupp, B. Engels, U. Diederichsen, Helv. Chim. Acta83, 2580 (2000). (10.1002/1522-2675(20000906)83:9<2580::AID-HLCA2580>3.0.CO;2-6) / Helv. Chim. Acta (2000)
F. Seela, C. Wei, A. Melenewski, E. Feiling, Nucleosides Nucleotides17, 2045 (1998). (10.1080/07328319808004745) / Nucleosides Nucleotides (1998)
H. Liu J. Gao L. Maynard D. Saito E. T. Kool in preparation.
R. F. Kauffman, H. A. Lardy, J. R. Barrio, M. C. G. Barrio, N. J. Leonard, Biochemistry17, 3686 (1978). (10.1021/bi00611a002) / Biochemistry (1978)
10.1038/343033a0
We thank N. J. Leonard for helpful discussions. This work was supported by NIH grants GM63587 and GM52956. H. L. and J. G. acknowledge support from Stanford Graduate Fellowships.

Dates

Type	When
Created	21 years, 10 months ago (Oct. 30, 2003, 8:25 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 10:22 p.m.)
Indexed	4 months, 3 weeks ago (April 10, 2025, 7:47 a.m.)
Issued	21 years, 10 months ago (Oct. 31, 2003)
Published	21 years, 10 months ago (Oct. 31, 2003)
Published Print	21 years, 10 months ago (Oct. 31, 2003)

Funders 0

None

BibTeX

@article{Liu_2003, title={A Four-Base Paired Genetic Helix with Expanded Size}, volume={302}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1088334}, DOI={10.1126/science.1088334}, number={5646}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Liu, Haibo and Gao, Jianmin and Lynch, Stephen R. and Saito, Y. David and Maynard, Lystranne and Kool, Eric T.}, year={2003}, month=oct, pages={868–871} }

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