Impact of modified ribose sugars on nucleic acid conformation and function

  title={Impact of modified ribose sugars on nucleic acid conformation and function},
  author={Marina G Evich and Alexander M. Spring-Connell and Markus W. Germann},
  journal={Heterocyclic Communications},
  pages={155 - 165}
Abstract The modification of the ribofuranose in nucleic acids is a widespread method of manipulating the activity of nucleic acids. These alterations, however, impact the local conformation and chemical reactivity of the sugar. Changes in the conformation and dynamics of the sugar moiety alter the local and potentially global structure and plasticity of nucleic acids, which in turn contributes to recognition, binding of ligands and enzymatic activity of proteins. This review article introduces… 

Figures and Tables from this paper

Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review.

This review systematically categorise various ribofuranose sugar modifications employed in DNAs and RNAs so far and discusses different stereoelectronic effects imparted by different substituents on the sugar ring and how these effects control sugar puckering.

Substituting Inosine for Guanosine in DNA: Structural and Dynamic Consequences

The fine structure of two hairpin DNA substrates that differ only in the substitution of an I-C base pair for a G-Cbase pair is determined using NMR restraints in conjunction with Mardigras and molecular dynamics.

The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides

A summary of structure and properties of artificial nucleic acids containing nucleobase, sugar or backbone modifications are presented, and an overview of the structure and mechanism of action of approved oligonucleotide drugs including gene silencing agents, aptamers and mRNA vaccines are provided.

Influence of 5-Methylation and the 2'- and 3'-Hydroxy Substituents on the Base Pairing Energies of Protonated Cytidine Nucleoside Analogue Base Pairs: Implications for the Stabilities of i-Motif Structures.

Results suggest that canonical DNA i-Motif conformations should be more stable than analogous RNA i-motif conformation and that 5-methylation of cytosine residues, a significant epigenetic marker, provides greater stabilization to DNA thanRNA i- Motif conformings.

Computational investigations of polymerase enzymes: Structure, function, inhibition, and biotechnology

The complex interaction of chemical and physical events during Pol catalysis, like metal‐aided enzymatic reactions for nucleotide addition and large conformational rearrangements for substrate selection and binding are examined.

Modification at the C2′-O-Position with 2-Methylbenzothiophene Induces Unique Structural Changes and Thermal Transitions on Duplexes of RNA and DNA

The findings describe methodology to attain unique structural motifs of modified duplexes of DNA or RNA, and control their behavior as a function of salt concentration.

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

The latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acy Clic, and conformationally biased nucleosides and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics are summarized.

Characteristic 1H NMR spectra of β-d-ribofuranosides and ribonucleosides: factors driving furanose ring conformations

A series of β-d-ribofuranosides and ribonucleosides fused with 2,3-O-isopropylidene ring was synthesized and studied in terms of their conformational preferences. Based on the 1H NMR spectra, DFT

Enzymatic Synthesis of 3'-5', 3'-5' Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations.

The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host

Detecting Biothreat Agents: From Current Diagnostics to Developing Sensor Technologies.

Although a fundamental understanding of the pathogenicity of most biothreat agents has been elucidated and available treatments have increased substantially over the past decades, they still



Recent Advances in Chemical Modification of Peptide Nucleic Acids

  • E. Rozners
  • Chemistry, Biology
    Journal of nucleic acids
  • 2012
Recent studies that improve on cellular uptake and binding of PNA to double-stranded DNA and RNA are discussed, focusing on chemical modifications of Pna's backbone and heterocyclic nucleobases.

A geometrical parametrization of C1'-C5' RNA ribose chemical shifts calculated by density functional theory.

An equation is presented that relates the structural parameters and the (13)C chemical shifts of the ribose group and represents a promising way of establishing quantitative and computationally efficient analytical relationships between chemical shifts and structural parameters in nucleic acids.

The importance of fitting in: conformational preference of selenium 2′ modifications in nucleosides and helical structures

This work provides a rationale why 2′-selenium modifications facilitate crystallization despite this contradictory behavior of selenium modification in a single nucleotide.

Selenium modification of nucleic acids: preparation of oligonucleotides with incorporated 2′-SeMe-uridine for crystallographic phasing of nucleic acid structures

This protocol describes a method for introducing an anomalously scattering atom into oligonucleotides at the 2′-position of uridine by conventional solid-phase synthesis to facilitate crystal structure determination for derivatization of RNA.

Structural Impact of Single Ribonucleotide Residues in DNA

The structures of three single‐ribonucleotide‐containing DNA duplexes and the corresponding DNA controls are reported, showing how a riboguanosine unit affects DNA in a distinct manner and manifests different hydrogen bonds, which makes generalizations difficult.

Scaffolding along nucleic acid duplexes using 2'-amino-locked nucleic acids.

Examples of this Account demonstrate that among other synthetic biopolymers, synthetic nucleic acids containing functionalized 2'-amino-LNA scaffolds offer great opportunities for material science, diagnostics, and medicine of the future.

Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Research conducted in the laboratory over the past two decades with a focus on crystal‐structure analyses of CNAs and artificial pairing systems is reviewed, highlighting key insights into issues ranging from conformational distortions as a consequence of modification to the modulation of pairing strength, and RNA affinity by stereoelectronic effects and hydration.

Structural basis of the RNase H1 activity on stereo regular borano phosphonate DNA/RNA hybrids.

It is predicted that on the basis of the NMR structures a fully R(P) BH(3) DNA/RNA hybrid would not be a substrate for RNase H1.

8-Oxoguanine Affects DNA Backbone Conformation in the EcoRI Recognition Site and Inhibits Its Cleavage by the Enzyme

It is proposed that the disruption of enzymatic cleavage can be linked with the altered backbone conformation and dynamics in the free oxidized DNA substrate and, possibly, at the protein—DNA interface.