scholarly journals Dioxaphosphorinane-Constrained Nucleic Acid Dinucleotides as Tools for Structural Tuning of Nucleic Acids

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Dan-Andrei Catana ◽  
Brice-Loïc Renard ◽  
Marie Maturano ◽  
Corinne Payrastre ◽  
Nathalie Tarrat ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Secondary Structure ◽  
Nucleic Acids ◽  
Polymer Structure ◽  
Rational Approach ◽  
Sugar Phosphate ◽  
Torsion Angles ◽  
Sugar Moiety ◽  
Phosphate Backbone ◽  
Structure Stabilization

We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion anglesαtoζdefining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers ofα,β-D-CNA exhibiting wether B-type canonical values or not.

scholarly journals Conformation-dependent restraints for polynucleotides: the sugar moiety

2019 ◽  
Vol 48 (2) ◽  
pp. 962-973
Author(s):  
Marcin Kowiel ◽  
Dariusz Brzezinski ◽  
Miroslaw Gilski ◽  
Mariusz Jaskolski
Keyword(s):  
Nucleic Acids ◽  
Crystal Structures ◽  
Protein Data Bank ◽  
Data Bank ◽  
Experimental Methods ◽  
Side Chain ◽  
Torsion Angles ◽  
Sugar Moiety ◽  
Structural Database ◽  
Different Parts

Abstract Stereochemical restraints are commonly used to aid the refinement of macromolecular structures obtained by experimental methods at lower resolution. The standard restraint library for nucleic acids has not been updated for over two decades and needs revision. In this paper, geometrical restraints for nucleic acids sugars are derived using information from high-resolution crystal structures in the Cambridge Structural Database. In contrast to the existing restraints, this work shows that different parts of the sugar moiety form groups of covalent geometry dependent on various chemical and conformational factors, such as the type of ribose or the attached nucleobase, and ring puckering or rotamers of the glycosidic (χ) or side-chain (γ) torsion angles. Moreover, the geometry of the glycosidic link and the endocyclic ribose bond angles are functionally dependent on χ and sugar pucker amplitude (τm), respectively. The proposed restraints have been positively validated against data from the Nucleic Acid Database, compared with an ultrahigh-resolution Z-DNA structure in the Protein Data Bank, and tested by re-refining hundreds of crystal structures in the Protein Data Bank. The conformation-dependent sugar restraints presented in this work are publicly available in REFMAC, PHENIX and SHELXL format through a dedicated RestraintLib web server with an API function.

scholarly journals Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4659 ◽  
Author(s):  
Steven Ochoa ◽  
Valeria T. Milam
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Chemical Structure ◽  
Chemical Diversity ◽  
Physiochemical Properties ◽  
Phosphate Backbone ◽  
Modified Nucleic Acids ◽  
Recent Developments ◽  
Diagnostic Applications

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.

scholarly journals Geometrical and Electronic Structure Variability of the Sugar−phosphate Backbone in Nucleic Acids

2008 ◽  
Vol 112 (27) ◽  
pp. 8188-8197 ◽  
Author(s):  
Daniel Svozil ◽  
Judit E. Šponer ◽  
Ivan Marchan ◽  
Alberto Pérez ◽  
Thomas E. Cheatham ◽  
...  
Keyword(s):  
Electronic Structure ◽  
Nucleic Acids ◽  
Sugar Phosphate ◽  
Phosphate Backbone

scholarly journals Convertible and Constrained Nucleotides: The 2’-Deoxyribose 5’-C-Functionalization Approach, a French Touch

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5925
Author(s):  
Crystalle Chardet ◽  
Corinne Payrastre ◽  
Béatrice Gerland ◽  
Jean-Marc Escudier
Keyword(s):  
Nucleic Acid ◽  
Conformational Space ◽  
Biological Applications ◽  
Sugar Phosphate ◽  
Conformationally Constrained ◽  
Precise Control ◽  
Phosphate Backbone ◽  
Nucleophilic Displacement ◽  
Torsional Angles ◽  
Biotechnical Properties

Many strategies have been developed to modulate the biological or biotechnical properties of oligonucleotides by introducing new chemical functionalities or by enhancing their affinity and specificity while restricting their conformational space. Among them, we review our approach consisting of modifications of the 5’-C-position of the nucleoside sugar. This allows the introduction of an additional chemical handle at any position on the nucleotide chain without disturbing the Watson–Crick base-pairing. We show that 5’-C bromo or propargyl convertible nucleotides (CvN) are accessible in pure diastereoisomeric form, either for nucleophilic displacement or for CuAAC conjugation. Alternatively, the 5’-carbon can be connected in a stereo-controlled manner to the phosphate moiety of the nucleotide chain to generate conformationally constrained nucleotides (CNA). These allow the precise control of the sugar/phosphate backbone torsional angles. The consequent modulation of the nucleic acid shape induces outstanding stabilization properties of duplex or hairpin structures in accordance with the preorganization concept. Some biological applications of these distorted oligonucleotides are also described. Effectively, the convertible and the constrained approaches have been merged to create constrained and convertible nucleotides (C2NA) providing unique tools to functionalize and stabilize nucleic acids.

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