ChemInform Abstract: From Anionic to Cationic α‐Anomeric Oligodeoxynucleotides

Abstract

Introduction: From b-to a-Anomery. -To obtain nuclease-resistant oligonucleotides that could be used as antisense for gene control, many modified oligonucleotides have been reported. Among them, in mid 80s oligodeoxynucleotides with an aanomeric configuration (a-ODNs) were synthesized, and their properties were evaluated (i.e., hybridization, nuclease resistance, and antisense activity). a-Anomeric nucleosides diverge from b-ones by an inversion of the configuration at C(1') anomeric position of the deoxyribofuranose ring. It was suggested on the basis of the Dreiding model study undertaken by Sequin as early as 1973 that a-ODNs could hybridize complementary b-DNA sequence but with a parallel orientation [1]. As shown in Fig. 1, b-thymidine 5'-monophosphate and a-thymidine 3'-monophosphate display the thymine base at the same place when the orientation is reversed. In this first publication, it was shown that TT dimers which exhibit one or two a-thymidines are resistant to phosphodiesterases.

Pyrrolidinyl PNA with α/β-Dipeptide Backbone: From Development to Applications

“…The effect of the pyrrolidine stereochemistry was next explored by employing (1 S ,2 S )-acpc as the spacer . Out of three remaining diastereomeric acpcPNAs, only the diastereomer with the (2′ R ,4′ S )-pyrrolidine/(1 S ,2 S )-acpc backbone (henceforth denoted as epi -acpcPNA) shows appreciable DNA binding affinity, which is only slightly lower than that of the acpcPNA having the (2′ R ,4′ R )-pyrrolidine/(1 S ,2 S )-acpc backbone (Figure ). , This behavior is analogous to that of α-anomeric DNA, which can form Watson–Crick pairs with normal (β) DNA …”

“…30,38 This behavior is analogous to that of αanomeric DNA, which can form Watson−Crick pairs with normal (β) DNA. 39 Importantly, decreasing the ring size of the cyclic β-amino acid spacer from five carbons in acpcPNA to four carbons in acbcPNA resulted in more stable PNA•DNA duplexes without compromising the base-pairing specificity, while achcPNA having a six-membered-ring spacer showed no ability to bind DNA. This can be rationalized by considering the NH−C2−C1−CO torsional angle (θ) in the cyclic β-amino acid (Figure 8).…”