Hydrogen-Bonding and π−π Base-Stacking Interactions Are Coupled in DNA, As Suggested by Calculated and Experimental Trans-Hbond Deuterium Isotope Shifts

Manalo, Marlon N.; Pérez, and Lisa M.; LiWang, Andy

doi:10.1021/ja0692940

Cited by 32 publications

(44 citation statements)

References 19 publications

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“…This research has revealed that deviations in these structural parameters are sequence dependent 7–10. Also, thermodynamic studies have suggested tentatively that hydrogen bonds and base‐stacking interactions are coupled in DNA11 and the measurements of the two‐bond deuterium isotope shift, 2 Δ 13 C,12 suggest that the hydrogen‐bond strengths in the DNA base pairs are modulated by the electronic interactions with adjacent bases to different extents depending on sequence context.…”

Section: Introductionmentioning

confidence: 92%

Theoretical Investigation of the Coupling between Hydrogen‐Atom Transfer and Stacking Interaction in Adenine–Thymine Dimers

Villani¹

2013

ChemPhysChem

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Three different dimers of the adenine-thymine (A-T) base pair are studied to point out the changes of important properties (structure, atomic charge, energy and so on) induced by coupling between the movement of the atoms in the hydrogen bonds and the stacking interaction. The comparison of these results with those for the A-T monomer system explains the role of the stacking interaction in the hydrogen-atom transfer in this biologically important base pair. The results support the idea that this coupling depends on the exact dimer considered and is different for the N-N and N-O hydrogen bonds. In particular, the correlation between the hydrogen transfer and the stacking interaction is more relevant for the N-N bridge than for the N-O one. Also, the two different mechanisms of two-hydrogen transfer (step by step and concerted) can be modified by the stacking interaction between the base pairs.

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Section: Introductionmentioning

confidence: 92%

Theoretical Investigation of the Coupling between Hydrogen‐Atom Transfer and Stacking Interaction in Adenine–Thymine Dimers

Villani¹

2013

ChemPhysChem

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“…The results indicate that upon substitution of T with Br U, a PNA·dsRNA triplex containing C + ·G-C base triples may become more resistant against high-pH destabilization. It is likely that enhancing hydrogen bonding and stacking involving X U·A-U base triples (compared to PNAs without X U substitution) may in turn favor C + ·G-C base triple formation and reduce the pH dependence by further shifting up the pK a of C residues in a PNA·dsRNA triplex through the coupling between stacking and hydrogen bonding interactions (78). However, the K d value of PNA FU-3,5 binding to rHP1 is still relatively pH dependent 0.3 and 4.7 M at pH 7.5 and 8.0, respectively), probably because F U stabilizes triplex formation mainly through enhancing base triple formation but not by shifting the pK a of adjacent C residues.…”

Section: Substitution Of T With U or Halouracils In An Unmodified Pnamentioning

confidence: 99%

“…Compared to P1, the singly-and doubly-modified PNA sequences have higher melting temperatures (based on the heating curves), with Cl U and Br U modifications being the most stabilizing ( Figure 4C, D). Compared to F U base, Cl U and Br U may be more ideal for optimizing the coupled stacking and hydrogen bonding interactions (78,79) for the sequences tested here, with the PNAs containing pyrimidine residues only. The stabilization effect of X U substitution on PNA-RNA duplex was also observed previously for a different PNA sequence (with the X U residue flanked by two G residues), although relatively less variation among F U, Br U, and Cl U was observed 5 (F, H).…”

Section: Substitution Of T With U or Halouracils In An Unmodified Pnamentioning

confidence: 99%

Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A–U pairs in dsRNAs

Patil

Toh

Yuan

et al. 2018

Nucleic Acids Research

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Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded RNA (ssRNA) regions and proteins, respectively, for diverse biological functions. Hence, targeting dsRNAs through major-groove triplex formation is a promising strategy for the development of chemical probes and potential therapeutics. Short (e.g., 6–10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind to dsRNAs sequence specifically at physiological conditions. For example, a PNA incorporating a modified base thio-pseudoisocytosine (L) has an enhanced recognition of a G–C pair in an RNA duplex through major-groove L·G–C base triple formation at physiological pH, with reduced pH dependence as observed for C+·G–C base triple formation. Currently, an unmodified T base is often incorporated into PNAs to recognize a Watson–Crick A–U pair through major-groove T·A–U base triple formation. A substitution of the 5-methyl group in T by hydrogen and halogen atoms (F, Cl, Br, and I) causes a decrease of the pKa of N3 nitrogen atom, which may result in improved hydrogen bonding in addition to enhanced base stacking interactions. Here, we synthesized a series of PNAs incorporating uracil and halouracils, followed by binding studies by non-denaturing polyacrylamide gel electrophoresis, circular dichroism, and thermal melting. Our results suggest that replacing T with uracil and halouracils may enhance the recognition of an A–U pair by PNA·RNA2 triplex formation in a sequence-dependent manner, underscoring the importance of local stacking interactions. Incorporating bromouracils and chlorouracils into a PNA results in a significantly reduced pH dependence of triplex formation even for PNAs containing C bases, likely due to an upshift of the apparent pKa of N3 atoms of C bases. Thus, halogenation and other chemical modifications may be utilized to enhance hydrogen bonding of the adjacent base triples and thus triplex formation. Furthermore, our experimental and computational modelling data suggest that PNA·RNA2 triplexes may be stabilized by incorporating a BrUL step but not an LBrU step, in dsRNA-binding PNAs.

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“…NMR spectroscopy is a particularly powerful tool for the study of H-bonding in biomolecules, which can be probed by chemical shifts, 21 NMR analysis of pressure-induced unfolding, 22 H-bond J-couplings, 23–27 H/D fractionation factors 28–32 and isotope shifts. 28, 33–34 …”

mentioning

confidence: 99%

Observation of α-Helical Hydrogen-Bond Cooperativity in an Intact Protein

Li¹,

Wang²,

Chen³

et al. 2016

J. Am. Chem. Soc.

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The presence and extent of hydrogen bonding cooperativity in proteins remains a fundamental question, which in the past has been studied extensively, mostly by infrared and fluorescence measurements on model peptides. We demonstrate that such cooperativity can be studied in an intact protein by hydrogen/deuterium exchange NMR spectroscopy. The method is based on the fact that substitution of NH by ND in a backbone amide group slightly weakens the N-H…O=C hydrogen bond. Our results show that such substitution at position i in an α-helix impacts the 1H and 15N chemical shifts of the amide sites of residues i − 3 to i + 3. Quantum mechanical calculations indicate that the upfield shifts of 1H and 15N resonances at site i, observed upon H/D exchanges at sites i − 3, i + 1, i + 2, and i + 3, correspond to a decrease of the ith backbone amide electric dipole moment, which weakens its hydrogen bonding and long range electrostatic interactions with other backbone amides in the α-helix. These results provide new quantitative insights into the cooperativity of H-bonding in protein α-helices.

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Hydrogen-Bonding and π−π Base-Stacking Interactions Are Coupled in DNA, As Suggested by Calculated and Experimental Trans-Hbond Deuterium Isotope Shifts

Cited by 32 publications

References 19 publications

Theoretical Investigation of the Coupling between Hydrogen‐Atom Transfer and Stacking Interaction in Adenine–Thymine Dimers

Theoretical Investigation of the Coupling between Hydrogen‐Atom Transfer and Stacking Interaction in Adenine–Thymine Dimers

Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A–U pairs in dsRNAs

Observation of α-Helical Hydrogen-Bond Cooperativity in an Intact Protein

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