Diastereoselective Synthesis of a Conformationally Restricted Dinucleotide with Predefined α and β Torsional Angles for the Construction of α,β-Constrained Nucleic Acids (α,β-CNA)

Abstract

[reaction: see text] The synthesis of a diastereopure 1,3,2-dioxaphosphorinane linkage in which two, alpha and beta, out of six torsion angles of the natural phosphodiester backbone are constrained with predefined values of ca. +60 degrees (g(+)) and 180 degrees (t), respectively, is described. The stable and unstrained six-membered cyclic phosphotriester structure represents the smallest possible ring allowing the conformational locking of the alpha torsion angle at a significant positive value that is typical of many bulged regions of nucleic acids.

α,β-D-Constrained Nucleic Acids Are Strong Terminators of Thermostable DNA Polymerases in Polymerase Chain Reaction

“…For this purpose, we used CNA to induce bending in the template. Since they were first synthesized [22], no published work has reported the functional impact of CNA on the behaviour of DNA polymerases. We used two different thermostable DNA polymerases in PCR: Pfu DNA polymerase and Taq DNA polymerase.…”

“…CNA are dinucleotide building blocks that can feature either B-type torsional angle values or non-canonical values, depending on their 5′C and P absolute stereochemistry (Fig. 1) [22], [23]. CNA display the gauche (+) conformation for the α torsional angle, which can induce destabilization of a duplex [24] as well as promote marked bending in a single-stranded DNA to preorganize it into a loop-like structure [25].…”

Dinucleotides containing two allyl groups by combinations of allyl phosphotriesters, 5-allyl-, 2′-O-allyl- and 2′-arabino-O-allyl uridine derivatives as substrates for ring-closing metathesis

“…15 Recently, another example of a conformationally restricted dinucleotide for this purpose with a linkage between the phosphate and the adjacent 5 0 -position has been introduced. 16 In all these cases, the covalent linkages have been obtained by conventional phosphoramidite chemistry, 17 disulfide bond formation and/or peptide/amide bond formation. 14- 16 We have concentrated on the development of a general methodology based on RCM for the construction of this type of conformationally restricted nucleic acid fragments.…”

“…16 In all these cases, the covalent linkages have been obtained by conventional phosphoramidite chemistry, 17 disulfide bond formation and/or peptide/amide bond formation. 14- 16 We have concentrated on the development of a general methodology based on RCM for the construction of this type of conformationally restricted nucleic acid fragments. Thus, we have synthesised a series of diastereomeric dinucleotides with phosphotriester internucleotide linkages containing seven-membered rings.…”

Sandwich probes: two simultaneous reactions for templated nucleic acid detection

“…1C; the 2-cyanoethyl group was purposely not cleaved from the 3′-phosphate group of the probe to reduce the probability of an intramolecular reaction between the phosphate and the quencher leaving group. 13 The presence of the three conjugated groups in the quenched probe, as well as the intact cyanoethyl group, was confirmed by MALDI-mass spectrometry (see ESI † ).…”