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

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.

2019 ◽  
Author(s):  
A. A. Icazatti ◽  
J.M. Loyola ◽  
I. Szleifer ◽  
J.A. Vila ◽  
O. A. Martin

ABSTRACTThe conformational space of the ribose–phosphate backbone is very complex as is defined in terms of six torsional angles. To help delimit the RNA backbone conformational preferences 46 rotamers have been defined in terms of the these torsional angles. In the present work, we use the ribose experimental and theoretical 13C′ chemical shifts data and machine learning methods to classify RNA backbone conformations into rotamers and families of rotamers. We show to what extent the use of experimental 13C′ chemical shifts can be used to identify rotamers and discuss some problem with the theoretical computations of 13C′ chemical shifts.


Biopolymers ◽  
2014 ◽  
Vol 101 (6) ◽  
pp. 640-650 ◽  
Author(s):  
Valeri Poltev ◽  
Victor M. Anisimov ◽  
Victor I. Danilov ◽  
Dolores Garcia ◽  
Carolina Sanchez ◽  
...  

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