Dynamics of a bis-intercalator DNA complex by 1H-detected natural abundance 13C NMR spectroscopy

H. Peter Spielmann

doi:10.1021/bi980789e

Dynamics of a bis-intercalator DNA complex by ¹H-detected natural abundance ¹³C NMR spectroscopy

H. Peter Spielmann

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32 Scopus citations

Abstract

The dynamics of the DNA oligomer d(CGCTAGCG)₂ (CTSYM) and its complex with the dye 1,1-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis-4-(3- methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO) (CTSYMTOTO) bis-intercalated at the 5'-CT-3' sequence steps have been determined from NMR relaxation parameters. Longitudinal and transverse ¹³C relaxation rates and heteronuclear NOE relaxation data were acquired and have been analyzed in the context of the Lipari and Szabo model- free formalism. The overall rotational correlation time for the CTSYM is 3.44 ns and the CTSYMTOTO is 3.48 ns. The generalized order parameters (S²) for methine carbons in the CTSYM and CTSYMTOTO are relatively high but nonuniform for the molecules and show sequence context and conformation-dependent variations. Average values of S² = 0.79 ± 0.02 for the CTSYM, S² = 0.80 ± 0.04 for the CTSYMTOTO aromatic spins, S² = 0.76 ± 0.02 for the CTSYM, and S² = 0.83 ± 0.05 for the CTSYMTOTO deoxyribose spins were found. The S² values for the 5'-terminal deoxyribose are lower than for the other residues. The DNA backbone in CTSYMTOTO is distorted and elongated at the site of intercalation, and the C3' atom of the C3 deoxyribose residue has a very low S² = 0.57 ± 0.06. The low order for this spin is interpreted in terms of exchange between the C2'-endo and O1'-endo conformations of the C3 deoxyribose. Significant chemical exchange processes were found for most of the aromatic spins in CTSYM that are interpreted in terms of microsecond to millisecond time scale dynamics. The microsecond to millisecond dynamics of the bases in CTSYM are quenched upon TOTO complex formation due to unwinding of the helix and an increase in the surface area of the bases in mutual contact and the large surface area in contact with the intercalated dye. The derived order parameters combined with the solution structure provide motional models for conformational changes induced in the backbone in response to the ligand binding.

Original language	English
Pages (from-to)	16863-16876
Number of pages	14
Journal	Biochemistry
Volume	37
Issue number	48
DOIs	https://doi.org/10.1021/bi980789e
State	Published - Dec 1 1998

ASJC Scopus subject areas

Biochemistry

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10.1021/bi980789e

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@article{f52b204a32ce49e5836a6f262f3c2b87,

title = "Dynamics of a bis-intercalator DNA complex by 1H-detected natural abundance 13C NMR spectroscopy",

abstract = "The dynamics of the DNA oligomer d(CGCTAGCG)2 (CTSYM) and its complex with the dye 1,1-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis-4-(3- methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO) (CTSYMTOTO) bis-intercalated at the 5'-CT-3' sequence steps have been determined from NMR relaxation parameters. Longitudinal and transverse 13C relaxation rates and heteronuclear NOE relaxation data were acquired and have been analyzed in the context of the Lipari and Szabo model- free formalism. The overall rotational correlation time for the CTSYM is 3.44 ns and the CTSYMTOTO is 3.48 ns. The generalized order parameters (S2) for methine carbons in the CTSYM and CTSYMTOTO are relatively high but nonuniform for the molecules and show sequence context and conformation-dependent variations. Average values of S2 = 0.79 ± 0.02 for the CTSYM, S2 = 0.80 ± 0.04 for the CTSYMTOTO aromatic spins, S2 = 0.76 ± 0.02 for the CTSYM, and S2 = 0.83 ± 0.05 for the CTSYMTOTO deoxyribose spins were found. The S2 values for the 5'-terminal deoxyribose are lower than for the other residues. The DNA backbone in CTSYMTOTO is distorted and elongated at the site of intercalation, and the C3' atom of the C3 deoxyribose residue has a very low S2 = 0.57 ± 0.06. The low order for this spin is interpreted in terms of exchange between the C2'-endo and O1'-endo conformations of the C3 deoxyribose. Significant chemical exchange processes were found for most of the aromatic spins in CTSYM that are interpreted in terms of microsecond to millisecond time scale dynamics. The microsecond to millisecond dynamics of the bases in CTSYM are quenched upon TOTO complex formation due to unwinding of the helix and an increase in the surface area of the bases in mutual contact and the large surface area in contact with the intercalated dye. The derived order parameters combined with the solution structure provide motional models for conformational changes induced in the backbone in response to the ligand binding.",

author = "Spielmann, {H. Peter}",

year = "1998",

month = dec,

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doi = "10.1021/bi980789e",

language = "English",

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number = "48",

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TY - JOUR

T1 - Dynamics of a bis-intercalator DNA complex by 1H-detected natural abundance 13C NMR spectroscopy

AU - Spielmann, H. Peter

PY - 1998/12/1

Y1 - 1998/12/1

N2 - The dynamics of the DNA oligomer d(CGCTAGCG)2 (CTSYM) and its complex with the dye 1,1-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis-4-(3- methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO) (CTSYMTOTO) bis-intercalated at the 5'-CT-3' sequence steps have been determined from NMR relaxation parameters. Longitudinal and transverse 13C relaxation rates and heteronuclear NOE relaxation data were acquired and have been analyzed in the context of the Lipari and Szabo model- free formalism. The overall rotational correlation time for the CTSYM is 3.44 ns and the CTSYMTOTO is 3.48 ns. The generalized order parameters (S2) for methine carbons in the CTSYM and CTSYMTOTO are relatively high but nonuniform for the molecules and show sequence context and conformation-dependent variations. Average values of S2 = 0.79 ± 0.02 for the CTSYM, S2 = 0.80 ± 0.04 for the CTSYMTOTO aromatic spins, S2 = 0.76 ± 0.02 for the CTSYM, and S2 = 0.83 ± 0.05 for the CTSYMTOTO deoxyribose spins were found. The S2 values for the 5'-terminal deoxyribose are lower than for the other residues. The DNA backbone in CTSYMTOTO is distorted and elongated at the site of intercalation, and the C3' atom of the C3 deoxyribose residue has a very low S2 = 0.57 ± 0.06. The low order for this spin is interpreted in terms of exchange between the C2'-endo and O1'-endo conformations of the C3 deoxyribose. Significant chemical exchange processes were found for most of the aromatic spins in CTSYM that are interpreted in terms of microsecond to millisecond time scale dynamics. The microsecond to millisecond dynamics of the bases in CTSYM are quenched upon TOTO complex formation due to unwinding of the helix and an increase in the surface area of the bases in mutual contact and the large surface area in contact with the intercalated dye. The derived order parameters combined with the solution structure provide motional models for conformational changes induced in the backbone in response to the ligand binding.

AB - The dynamics of the DNA oligomer d(CGCTAGCG)2 (CTSYM) and its complex with the dye 1,1-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis-4-(3- methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinolinium tetraiodide (TOTO) (CTSYMTOTO) bis-intercalated at the 5'-CT-3' sequence steps have been determined from NMR relaxation parameters. Longitudinal and transverse 13C relaxation rates and heteronuclear NOE relaxation data were acquired and have been analyzed in the context of the Lipari and Szabo model- free formalism. The overall rotational correlation time for the CTSYM is 3.44 ns and the CTSYMTOTO is 3.48 ns. The generalized order parameters (S2) for methine carbons in the CTSYM and CTSYMTOTO are relatively high but nonuniform for the molecules and show sequence context and conformation-dependent variations. Average values of S2 = 0.79 ± 0.02 for the CTSYM, S2 = 0.80 ± 0.04 for the CTSYMTOTO aromatic spins, S2 = 0.76 ± 0.02 for the CTSYM, and S2 = 0.83 ± 0.05 for the CTSYMTOTO deoxyribose spins were found. The S2 values for the 5'-terminal deoxyribose are lower than for the other residues. The DNA backbone in CTSYMTOTO is distorted and elongated at the site of intercalation, and the C3' atom of the C3 deoxyribose residue has a very low S2 = 0.57 ± 0.06. The low order for this spin is interpreted in terms of exchange between the C2'-endo and O1'-endo conformations of the C3 deoxyribose. Significant chemical exchange processes were found for most of the aromatic spins in CTSYM that are interpreted in terms of microsecond to millisecond time scale dynamics. The microsecond to millisecond dynamics of the bases in CTSYM are quenched upon TOTO complex formation due to unwinding of the helix and an increase in the surface area of the bases in mutual contact and the large surface area in contact with the intercalated dye. The derived order parameters combined with the solution structure provide motional models for conformational changes induced in the backbone in response to the ligand binding.

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Dynamics of a bis-intercalator DNA complex by ¹H-detected natural abundance ¹³C NMR spectroscopy

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