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Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

Dieter Buyst (UGent) , Vicky Gheerardijn (UGent) , Krisztina Fehér (UGent) , Björn Van Gasse (UGent) , Jos Van den Begin (UGent) , José Martins (UGent) and Annemieke Madder (UGent)
(2015) NUCLEIC ACIDS RESEARCH. 43(1). p.51-62
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Abstract
The predictable 3D structure of double-stranded DNA renders it ideally suited as a template for the bottom-up design of functionalized nucleic acid-based active sites. We here explore the use of a 14mer DNA duplex as a scaffold for the precise and predictable positioning of catalytic functionalities. Given the ubiquitous participation of the histidine-based imidazole group in protein recognition and catalysis events, single histidine-like modified duplexes were investigated. Tethering histamine to the C5 of the thymine base via an amide bond, allows the flexible positioning of the imidazole function in the major groove. The mutual interactions between the imidazole and the duplex and its influence on the imidazolium pKa(H) are investigated by placing a single modified thymine at four different positions in the center of the 14mer double helix. Using NMR and unrestrained molecular dynamics, a structural motif involving the formation of a hydrogen bond between the imidazole and the Hoogsteen side of the guanine bases of two neighboring GC base pairs is established. The motif contributes to a stabilization against thermal melting of 6 degrees C and is key in modulating the pKa(H) of the imidazolium group. The general features, prerequisites and generic character of the new pKa(H)-regulating motif are described.
Keywords
Molecular Dynamics, Modified DNA, Imidazole, NMR, MOLECULAR-DYNAMICS SIMULATIONS, PARTICLE MESH EWALD, LOOP-HELIX MOTIF, NMR-SPECTROSCOPY, NUCLEIC-ACIDS, B-DNA, AMINO FUNCTIONALITIES, BASE MISMATCHES, RNA LIGANDS, SELECTION

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MLA
Buyst, Dieter, et al. “Identification of a PKa-Regulating Motif Stabilizing Imidazole-Modified Double-Stranded DNA.” NUCLEIC ACIDS RESEARCH, vol. 43, no. 1, 2015, pp. 51–62, doi:10.1093/nar/gku1306.
APA
Buyst, D., Gheerardijn, V., Fehér, K., Van Gasse, B., Van den Begin, J., Martins, J., & Madder, A. (2015). Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA. NUCLEIC ACIDS RESEARCH, 43(1), 51–62. https://doi.org/10.1093/nar/gku1306
Chicago author-date
Buyst, Dieter, Vicky Gheerardijn, Krisztina Fehér, Björn Van Gasse, Jos Van den Begin, José Martins, and Annemieke Madder. 2015. “Identification of a PKa-Regulating Motif Stabilizing Imidazole-Modified Double-Stranded DNA.” NUCLEIC ACIDS RESEARCH 43 (1): 51–62. https://doi.org/10.1093/nar/gku1306.
Chicago author-date (all authors)
Buyst, Dieter, Vicky Gheerardijn, Krisztina Fehér, Björn Van Gasse, Jos Van den Begin, José Martins, and Annemieke Madder. 2015. “Identification of a PKa-Regulating Motif Stabilizing Imidazole-Modified Double-Stranded DNA.” NUCLEIC ACIDS RESEARCH 43 (1): 51–62. doi:10.1093/nar/gku1306.
Vancouver
1.
Buyst D, Gheerardijn V, Fehér K, Van Gasse B, Van den Begin J, Martins J, et al. Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA. NUCLEIC ACIDS RESEARCH. 2015;43(1):51–62.
IEEE
[1]
D. Buyst et al., “Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA,” NUCLEIC ACIDS RESEARCH, vol. 43, no. 1, pp. 51–62, 2015.
@article{5802422,
  abstract     = {{The predictable 3D structure of double-stranded DNA renders it ideally suited as a template for the bottom-up design of functionalized nucleic acid-based active sites. We here explore the use of a 14mer DNA duplex as a scaffold for the precise and predictable positioning of catalytic functionalities. Given the ubiquitous participation of the histidine-based imidazole group in protein recognition and catalysis events, single histidine-like modified duplexes were investigated. Tethering histamine to the C5 of the thymine base via an amide bond, allows the flexible positioning of the imidazole function in the major groove. The mutual interactions between the imidazole and the duplex and its influence on the imidazolium pKa(H) are investigated by placing a single modified thymine at four different positions in the center of the 14mer double helix. Using NMR and unrestrained molecular dynamics, a structural motif involving the formation of a hydrogen bond between the imidazole and the Hoogsteen side of the guanine bases of two neighboring GC base pairs is established. The motif contributes to a stabilization against thermal melting of 6 degrees C and is key in modulating the pKa(H) of the imidazolium group. The general features, prerequisites and generic character of the new pKa(H)-regulating motif are described.}},
  author       = {{Buyst, Dieter and Gheerardijn, Vicky and Fehér, Krisztina and Van Gasse, Björn and Van den Begin, Jos and Martins, José and Madder, Annemieke}},
  issn         = {{0305-1048}},
  journal      = {{NUCLEIC ACIDS RESEARCH}},
  keywords     = {{Molecular Dynamics,Modified DNA,Imidazole,NMR,MOLECULAR-DYNAMICS SIMULATIONS,PARTICLE MESH EWALD,LOOP-HELIX MOTIF,NMR-SPECTROSCOPY,NUCLEIC-ACIDS,B-DNA,AMINO FUNCTIONALITIES,BASE MISMATCHES,RNA LIGANDS,SELECTION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{51--62}},
  title        = {{Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA}},
  url          = {{http://dx.doi.org/10.1093/nar/gku1306}},
  volume       = {{43}},
  year         = {{2015}},
}

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