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Sideritis species have been used in folk medicine for their antimicrobial, antiulcerogenic, digestive and anti-inflammatory properties. Over the years, the phytochemistry of the genus Sideritis has been studied, and various terpenoids, sterols, coumarins and especially flavonoid aglycones and glycosides have been identified. In particular, species from the Balkan Peninsula have been studied and were found to be rich in flavonoids, with valuable antioxidant activity. In the folk medicine of the Balkan countries, Sideritis raeseri is used as a herbal tea in the treatment of inflammation, gastrointestinal disorders and coughs, and also as a tonic, whereas extracts are used as a component of dietary supplements for anaemia. Its dried inflorescences are used to prepare a beverage called ‘mountain tea’. In light of the considerable interest generated in the chemistry, pharmacological properties and commercial value of S. raeseri Boiss. & Heldr., we review and summarise the available literature on these plants. The review details the chemical composition of the essential oil, its mineral and polyphenol contents, the naming of these plants and their physicochemical characterisation, and the nuclear magnetic resonance spectral data and biological properties associated with the plant extracts, with a focus on their potential chemotherapeutic applications.

Phosphoramidite I (1, R = iPr) useful as phosphorylation reagent in oligonucleotide syntheses, were prepd. by monomethoxytrityl protection of 4-​hydroxybenzaldehyde with subsequent borohydride redn. and phosphorylation with 2-​cyanomethyl N,​N-​diisopropylphosphoroamidochloridite. In an example, reaction of 5.08 g of 4-​hydroxybenzaldehyde with 1.0 g of 4-​methoxytriphenylmethyl chloride in 10 mL of dichloromethane in the presence of 2.2 mL of EtNiPr2 at 20° for 6 h gave the protected benzaldehyde, which was reduced with 0.25 g of NaBH4 in 10 mL of THF for 6 h at 20°, giving the protected benzyl alc., 4-​MMTO-​C6H4CH2OH with 85​% yield. The obtained product (0.23 g) was reacted with 0.2 mL of phosphoramidochloridite NCCH2CH2OP(Cl)​NiPr2in the presence of 0.4 mL of EtNiPr2 in 5 mL of CH2Cl2, giving the product 1 with 87​% yield.

RNA interference (RNAi) is a biological process whereby small interfering RNA (siRNA) and microRNA (miRNA) silence gene expression in a sequence-specific manner. These effectors regulate gene expression through the RNA-induced silencing complex (RISC). It has been suggested that RISC preferentially selects and incorporates one of two strands of the siRNA duplex depending on its thermodynamic features and that the off-target effects of siRNAs can be correlated to the Tm of the duplex. The problem of unwanted incorporation of the passenger strand into RISC could be address altering the thermodynamic asymmetry of the duplex by using specific chemical modifications. Structural studies have revealed that the 3’-overhang region of the guide strand of siRNA is recognized by the PAZ domain and is accommodated into its hydrophobic binding pocket. We expected that aromatic-based modifications in 3’-overhang would enhance RISC selection of antisense strands of siRNA duplexes, reducing off-target effects induced by sense strands. In this study, we report the synthesis of siRNAs bearing diphenylpropylamine, tyramine and tryptamine units at the 3’-end of sense and antisense strands. We found thermodynamic stability of the conjugates was increased by these modifications. Furthermore, but not surprisingly, the modified duplexes were found to retain RNA-like A-type conformation. We also assessed the nuclease resistance of the modified siRNAs and found it was similar to those of unmodified siRNAs. These results prompted us to investigate the silencing activity of the siRNAs possessing the aromatic moiety in the 3’-end by in vitro experiments in mammalian cells.

Several G-rich synthetic oligodeoxyribonucleotides (ODNs) have shown promising biological properties, ranging from anticancer to anti-HIV activities. G-quadruplex formation was found to be a crucial prerequisite in determining these biological effects. Aptamers exhibiting anti-HIV activity represent an important class of potential therapeutics. Recently we described the synthesis and characterization of new d(TGGGAG) ODNs, conjugated with different aromatic groups at the 5’-end through a phosphodiester bond. The modified sequences showed a parallel stranded tetramolecular G-quadruplexes CD profile and a pronounced anti-HIV-1 activity. Herein, with the aim to use d(TGGGAG) as a lead sequence for a more effective anti-HIV agent, we propose the fully automated synthesis of new ODNs containing two d(TGGGAG) sequences whose 3-ends are joint by an hexaethylenglycole loop. CD analysis was undertaken on the 3’-3’ linked d(TGGGAG) hairpins in comparison with the corresponding unmodified oligomers. Besides, in order to study the influence of the conjugation at the ends of the harpin chains on their ability to stabilize quadruplex structures and on their anti-HIV activity, different conjugated oligomers have been studied.

CyPLOS (cyclic phosphate-linked oligosaccharides), that is, novel cyclic oligosaccharide surrogates, consisting of two, three, and four phenyl-â-D-glucopyranoside units, 4,6-linked through stable phosphodiester bonds, were prepared by a straightforward and efficient solid-phase protocol. The assembly of the linear precursors was achieved by standard phosphoramidite chemistry on an automated DNA synthesizer, using a suitably protected 4-phosphoramidite derivative of D-glucose as the building block. For the crucial cyclization step a phosphotriester methodology was exploited, followed by a mild basic treatment releasing the desired cyclic molecules in solution in a highly pure form. The cyclic dimer and trimer were also independently prepared by classical solution synthesis, basically following the same approach. The solution structural preferences of the cyclic dimer and trimer, obtained by detailed NMR analysis, are also reported.

A convenient solid-phase synthesis of oligonucleotides conjugated at the 3'-end with a tetraphenylporphyrin residue, by means of a new polymeric support bearing as a linker a lysine derivative, has been developed. A porphyrin linked 17-mer, designed for antisense experiments, has been prepared in good yields, and its hybridization properties with a complementary DNA fragment evaluated by UV thermal analysis.

We have described the fully automated syntehsis of ppetide-glycoconjugates. Test of activity was also done.

New solid supports, functionalized with suitably protected 1,2,3-propanetriol and cis,cis-1,3,5-cyclohexanetriol, were efficiently prepared and used in the standard automated synthesis of 3′-3′ linked ODNs for triplex formation experiments.

The solid-phase synthesis of 3'-derivatized oligonucleotides, by using a support which links the first nucleoside-3'-phosphate through the nucleobase, is reported. Following this procedure, the marking molecules can easily incorporated in satisfactory yields at the 3'-phosphate terminus either before or after the chain assembly.