## 6 Serinol Nucleic Acids (SNA)
Upon hybridization with the target strand, the fluorophores intercalate, and the quenching does not occur, resulting in fluorescence emission at \(\lambda\approx\) 490 nm of the perylene molecules. Finally, a quencher-free linear SNA probe containing three \({}^{\text{Pe}}\)U units, each separated by six nucleobases, was synthesized, allowing detection of target RNA with high sensitivity and discrimination of a single-base mismatch. The differences in fluorescence were visible to the naked eye, as the single strand had yellow emission, the fully matched duplex emitted bright green light and the mismatched duplex emitted faint green fluorescence. The SNA scaffold has been successfully used to prepare molecular beacons (SNA-MB) bearing a fluorophore (perylene or Cy3) and the anthraquinone quencher at opposite ends [75]. Both fluorophore/quencher pairs worked well, and strong fluorescence emissions were observed for complementary target RNAs, almost equal to those of a single strand carrying only the fluorophore. A signal-to-noise ratio of up to 930 was observed for the perylene/anthraquinone pair. Fluorescence measurements in the lysate of HeLa cells showed that the SNA-MBs were resistant to degradation by nuclease and the probes could be used to visualize mRNA in fixed cells. It was found that SNA-type nucleotides could enhance the efficacy of oligomers acting in the RNA interference process. In the dual luciferase assay, an siRNA duplex and its analogs modified with 1, 3, 5 or 7 SNA nucleotides at each of the sense strands or at the 3\({}^{\prime}\) end of the antisense strand were prepared [76]. PAGE Analysis of the products of incubation of siRNAs with cell lysate showed that the increasing number of SNA modifications led to a deterioration of siRNA stability. For example, a duplex with seven modifications at each end of the passenger strand and at the 3\({}^{\prime}\)-end of the guide strand was largely hydrolyzed after only 1 min of incubation. Moreover, RNAi activity decreased with increasing number of SNA substitutions on the antisense strand. The authors conclude that substitutions of an SNA residue at each end of the passenger strand and at the 3\({}^{\prime}\)-end of the antisense strand were most effective, as they conferred the best resistance to nucleolytic degradation and virtually eliminated incorporation of the sense strand into the RISC complex without inhibiting silencing activity. The aforementioned phenomenon that SNA molecules of palindromic sequences are achiral was the basis for the construction of a nanowire that functions as a helical amplification system [77]. The nanowires were formed by hybridizing the palindromic SNA oligomers (\(S\))-TCGTCCTGCT-(\(R\)) and (\(R\))-GACGAAGCAG-(\(S\)), which are partially complementary across the underlined segments. The duplexes possessed 5-nt overhangs--AGCAG-(\(S\)) and (\(S\))-TCGTC--and used these to continue hybridization. Atomic force spectroscopy of the resulting nanowires revealed an average length of 53.6 nm. Melting analysis revealed Tm = 46.7 \({}^{\circ}\)C, indicating that the complex is stable at room temperature. The CD measurement performed for the fully complementary SNA duplex (\(S\))-TCGTCCTGCT-(\(R\))/(\(R\))-AGCAGAGCAG-(\(S\)), which should be achiral due to the palindromic sequence, showed only very weak signals, if any. The CD spectra changed completely when even small amounts (0.01 eq) of D-aTNA or L-aTNA oligomers 1\({}^{\prime}\)- TCGTCCTC-3\({}^{\prime}\) were added. The CD spectra had a negative peak at about 260 nm and a positive peak at about 285 nm, or a positive peak at 260 nm and a negative peak at 285 nm, respectively. Interestingly, the intensities increased with the number of equivalents of the given aTNA oligomer, but a plateau was reached after the addition of 0.2 equivalents. While amplitudes of 15 mdeg were detected in these experiments, the amplitudes of the CD signals increased linearly (no plateau) for the fully complementary duplex (\(S\))-TCGTCCTGCT-(\(R\))/(\(R\))-AGCAGAGAGAG-(\(S\)) and did not exceed 6 mdeg.