title: NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.
abstract: Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.
authors: Department of Chemistry, University of Paderborn, Warburger Str. 100, 33 098 Paderborn, Germany ; Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66 123 Saarbrücken, Germany.
authors: Boris
authors: B
authors: Schmidtgall
authors: Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37 077 Göttingen, Germany ; Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37 077 Göttingen, Germany.
authors: Claudia
authors: C
authors: Höbartner
authors: Department of Chemistry, University of Paderborn, Warburger Str. 100, 33 098 Paderborn, Germany ; Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66 123 Saarbrücken, Germany.
authors: Christian
authors: C
authors: Ducho
keywords: DNA; backbone modifications; nucleic acids; oligonucleotides; stereoselective synthesis; zwitterions