This article describes the synthesis of 3'/5' linked 1,2,3-triazolyl dithymidine derivatives, their incorporation into oligonucleotides, and evaluation of their thermal stabilities toward complementary DNA/RNA.
[structures: see text] A serious drawback of peptide nucleic acids (PNAs) from an application perspective that has not been adequately dealt with is nondiscrimination of identical DNA and RNA sequences. An analysis of the available X-ray and NMR solution structures of PNA complexes with DNA and RNA suggested that it might be possible to rationally impart DNA/RNA duplex binding selectivity by tuning the dihedral angle beta of the flexible ethylenediamine part of the PNA backbone (II) via suitable chemical modifications. Cyclohexanyl PNAs (chPNAs) with beta approximately = 65 degrees were designed on the basis of this rationale. The chPNAs introduced remarkable differences in duplex stabilities among their DNA and RNA complexes, with melting temperatures (deltaTm(RNA-DNA) = +16-50 degrees C) depending on the number of modifications and the stereochemistry. This is a highly significant, exceptional binding selectivity of a mix sequence of PNA to RNA over the same DNA sequence as that seen to date. In contrast, cyclopentanyl PNAs (cpPNAs) with beta approximately = 25 degrees hybridize to DNA/RNA strongly without discrimination because of the ring puckering of the cyclopentane ring. The high affinity of chPNAs to bind to RNA without losing base specificity will have immediate implications in designing improved PNAs for therapeutic and diagnostic applications.
A simple method for the synthesis of a sugar furanoid trans vicinal diacid and its incorporation into the N-terminal tetrapeptide sequence (H-Phe-Trp-Lys-Thr-OH) to get glycopeptide has been described. 2D NMR and MD simulation studies of clearly show that the sugar diacid adopts a γ-turn conformation towards the N-terminus.
SummaryThe TMSOTf-mediated synthesis of β-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a “Ritter-like” reaction in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-β-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group.
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