Abstract

Many recent developments in solid-state NMR of quadrupolar nuclei allow for the direct study of quadrupolar nuclei in biological macromolecules. We have carried out a 2'Na NMR study of guanine-rich DNA oligonucleotides that associate to form G-quadruplexes. DNA quadruplexes have been proposed to form at the ends of telomeres, the physical end of chromosomes. DNA quadruplexes have also recently attracted interest as potential targets for anticancer drugs. The guanines in the quadruplexes form G-quartets and the structures are stabilized by coordination of monovalent cations such as sodium and potassium to the carbonyl oxygens in the center of the quartets. We have performed 2'Na NMR on the tetrameric 'and dimeric quadruplexes formed by [d(TG4T)]4 and [d(G4T4G4)]2, respectively, to identify and assign the multiple cation binding sites in the center of the quadruplexes. We use high field strengths (17.6T) and several 2D methods to obtain valuable resolution, connectivi ty informa tion and assignments, allowing us to distinguish between channel, surface and free sodium ions.
We aim to clarify the mechanism of competitive exchange of sodium with other cations to better understand the stabilization of DNA quadruplexes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-25
Application #
6355123
Study Section
Project Start
2000-05-01
Project End
2001-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
25
Fiscal Year
2000
Total Cost
$17,121
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

Showing the most recent 10 out of 12 publications