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Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution.

Publication ,  Journal Article
Nikolova, EN; Gottardo, FL; Al-Hashimi, HM
Published in: J Am Chem Soc
February 29, 2012

Nucleic acids transiently morph into alternative conformations that can be difficult to characterize at the atomic level by conventional methods because they exist for too little time and in too little abundance. We recently reported evidence for transient Hoogsteen (HG) base pairs in canonical B-DNA based on NMR carbon relaxation dispersion. While the carbon chemical shifts measured for the transient state were consistent with a syn orientation for the purine base, as expected for A(syn)•T(anti) and G(syn)•C(+)(anti) HG base pairing, HG type hydrogen bonding could only be inferred indirectly. Here, we develop two independent approaches for directly probing transient changes in N-H···N hydrogen bonds and apply them to the characterization of transient Hoogsteen type hydrogen bonds in canonical duplex DNA. The first approach takes advantage of the strong dependence of the imino nitrogen chemical shift on hydrogen bonding and involves measurement of R(1ρ) relaxation dispersion for the hydrogen-bond donor imino nitrogens in G and T residues. In the second approach, we assess the consequence of substituting the hydrogen-bond acceptor nitrogen (N7) with a carbon (C7H7) on both carbon and nitrogen relaxation dispersion data. Together, these data allow us to obtain direct evidence for transient Hoogsteen base pairs that are stabilized by N-H···N type hydrogen bonds in canonical duplex DNA. The methods introduced here greatly expand the utility of NMR in the structural characterization of transient states in nucleic acids.

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Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

February 29, 2012

Volume

134

Issue

8

Start / End Page

3667 / 3670

Location

United States

Related Subject Headings

  • Nucleic Acid Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Hydrogen Bonding
  • General Chemistry
  • DNA
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

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Nikolova, E. N., Gottardo, F. L., & Al-Hashimi, H. M. (2012). Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution. J Am Chem Soc, 134(8), 3667–3670. https://doi.org/10.1021/ja2117816
Nikolova, Evgenia N., Federico L. Gottardo, and Hashim M. Al-Hashimi. “Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution.J Am Chem Soc 134, no. 8 (February 29, 2012): 3667–70. https://doi.org/10.1021/ja2117816.
Nikolova EN, Gottardo FL, Al-Hashimi HM. Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution. J Am Chem Soc. 2012 Feb 29;134(8):3667–70.
Nikolova, Evgenia N., et al. “Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution.J Am Chem Soc, vol. 134, no. 8, Feb. 2012, pp. 3667–70. Pubmed, doi:10.1021/ja2117816.
Nikolova EN, Gottardo FL, Al-Hashimi HM. Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution. J Am Chem Soc. 2012 Feb 29;134(8):3667–3670.
Journal cover image

Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

February 29, 2012

Volume

134

Issue

8

Start / End Page

3667 / 3670

Location

United States

Related Subject Headings

  • Nucleic Acid Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Hydrogen Bonding
  • General Chemistry
  • DNA
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences