## 6 Serinol Nucleic Acids (SNA)  
Compared to aTNA, the acyclic flexible scaffold of serinol nucleic acids (**33**, Chart 10, a dinucleotide is shown) does not contain a methyl group (in the position next to the amino group), which gives rise to the phenomenon of two stereogenic centers in the aTNA unit [68]. Thus, the chirality of the SNA molecule synthesized from four SNA monomers depends only on its sequence. The chirality of oligomers is denoted by (\(R\)) and (\(S\)) descriptors assigned to each end according to the chirality of the terminal residues. If the sequence is palindromic (e.g., ATTGCGTTA or pATTGCGTTAp), the entire molecule is achiral, although there is a carbon atom with four different substituents in each SNA unit except the central one. When an oligomer has an odd number of SNA units (e.g., ApTpTpGpCGpTpPA), the plane of symmetry passes through the central carbon atom of the backbone within the central SNA unit, which is SNA-C in this example. When this number is even (e.g., ApTpTpGpGpTpTpA), the symmetry plane passes through the central phosphorus atom, which is marked as underlined. In both cases, these are the _meso_ forms. When a sequence is non-palindromic (e.g., ATTGCGTAA, pATTGCGTTA or ATTGCGTTAp), the molecule is chiral. Four chiral SNA-phosphoridite monomers **35** were synthesized by condensation of the carboxymethyl derivatives of nucleobases (A\({}^{\text{Bz}}\), T, G\({}^{\text{IBu}}\) or C\({}^{\text{Bz}}\)) with the amino group of amino alcohol **34** (Scheme 7) obtained from L-serine. The procedure used for the synthesis of the DMT-protected amino alcohol [69] allowed to obtain enantiomerically pure compounds, which were used for the synthesis of seven SNA-octamers. Their combinations should yield chiral antiparallel, chiral parallel and achiral duplexes. In addition, DNA and RNA oligomers isosequential with the SNA oligomers were prepared, and the thermal stability of SNA, DNA and RNA homoduplexes, as well as SNA/DNA and SNA/RNA heteroduplexes, was determined. The melting experiments showed that not only were the expected antiparallel SNA homoduplexes formed (Tm = 51 \({}^{\circ}\)C), but also the parallel ones, although the latter were much less stable (Tm = 16 \({}^{\circ}\)C). Importantly, however, the antiparallel SNA/SNA duplexes were much more stable than the isosequential DNA/DNA (Tm = 23 or 29 \({}^{\circ}\)C) or RNA/RNA (Tm = 38 or 39 \({}^{\circ}\)C) complexes. It should be emphasized that SNA oligomers formed antiparallel heteroduplexes with DNA and RNA matrices whose stability was only a few degrees lower than that of the DNA/DNA (20-24 vs. 23-29 \({}^{\circ}\)C) and RNA/RNA (32-36 vs. 38-39 \({}^{\circ}\)C) homoduplexes. Analogously to the previously described L-aTNA/RNA duplex [59], a crystal structure showed that an SNA/RNA duplex adopts right-handed helicity and uses the Watson-Crick base-pairing. Two pairs of the synthesized oligomers were of inverted sequences, so they constituted two pairs of enantiomeric species. They were designed to answer a question about the possible helicity of the corresponding enantiomeric duplexes. Indeed, the corresponding CD spectra showed exactly inverse signals, confirming the existence of right- and left handed helices, and the handedness depended on the sequences. The spectrum recorded for the symmetric achiral duplex showed no induced CD signals. To increase the thermal stability of the SNA/RNA duplexes, the adenine moieties were replaced with 2,6-diaminopurine (D), which forms a D:U pair (**36**, Chart 11) with uracil with three hydrogen bonds [70]. While the melting experiment for a DNA/RNA duplex 5\({}^{\prime}\)-d(CAACATCAGTCTGAT AAGCTA)-3\({}^{\prime}\)/5\({}^{\prime}\)-UAGCUUAUGAGACUGAUGUG-3\({}^{\prime}\) yielded Tm = 57 \({}^{\circ}\)C, this parameter increased to 67 \({}^{\circ}\)C for the isosequential SNA/RNA duplex, and Tm = 76 \({}^{\circ}\)C was observed for the SNA/RNA analog in which CDDCDTCDGTCTGDDTDGCTA was the SNA component.