Nucleic acid analog

Takemoto, K. and Inaki, Y. Synthetic Nucleic Acid Analogs. Preparation and Interactions. Vol. 41, pp. 1-51. 

Fig. 1 Chemical structures of backbone modifications used in therapeutic nucleic acid analogs. Shown are the unmodified DNA/RNA chemical structures in addition to a selection of first (PS), second (OMe, MOE), and third generation (PNA, LNA, MF) nucleic acid modifications...

Use of Cl2(PCy3)2RuCHPh for the Synthesis of Thymine-Substituted Polymers as Potential Nucleic Acid Analogs... 

The investigations directed at the synthesis of thymine-substituted polymers demonstrate that the type of functional groups displayed by nucleic acid bases are compatible with ROMP. Moreover, the application of MALDI-TOF mass spectrometry to the analysis of these polymers adds to the battery of tools available for the characterization of ROMP and its products. The utility of this approach for the creation of molecules with the desired biological properties, however, is still undetermined. It is unknown whether these thymine-substituted polymers can hybridize with nucleic acids. Moreover, ROMP does not provide a simple solution to the controlled synthesis of materials that display specific sequences composed of all five common nucleic acid bases. Nevertheless, the demonstration that metathesis reactions can be conducted with such substrates suggests that perhaps neobiopolymers that function as nucleic acid analogs can be synthesized by such processes. 

The chemistry of nucleic acid analogs has received much attention in recent years, and a series of nucleic acid models has been designed and widely prepared, in order to estimate and utilize their functionalities in relation to the specific basepairing properties ( J., i, ). These monomers and polymers, particularly those containing purines, pyrimidines, nucleosides, and nucleotides, are not only of interest to the field of heterocyclic organic chemistry, but also to that of biomimetic macro-molecular chemistry as synthetic analogs of the nucleic acids. 

In addition to stabilizing appendages, dynamic nucleic acid modification has been applied in supramolecular chemistry to develop novel materials. To this end, Lehn and coworkers developed dynamic nucleic acid analogs,... 

A synthesis of the monomeric unit 128 of a peptide nucleic acid analog (PNA) offers an example of stereospecific cross-coupling of a Reformatsky reagent with (Z)-vinylic iodide 126. The coupling reaction of the preformed Reformatsky reagent prepared in dimethoxymethane (methylal) with 126 is carried out using 8% of Pd(PPh3)4 in DMPU as the solvent at 65 °C to afford 127 (equation 70)161. 

Nucleic Acid Analogs and Polyanionic Polymers as Polymer Drug - 127... 

Among the nucleic acid analogs prepared so far, vinyl type polymers bearing nucleic acid bases such as poly(VAd) are known to form a strong complex with a naturally occurring nucleic acid in an aqueous medium [57-59], As shown in Scheme 8, 9-vinyladenine (VAd) monomer was prepared conveniently in a high... 

Consequently, both nucleic acid analogs such as poly(VAd) and pharmaceutically active syntetic polyanionic polymers having hydrophobic moieties may interact with nucleic acids in vivo. 

Several pharmaceutical activities of nucleic acid analogs such as poly(VAd) have been studied in vitro and in cell-free systems [19]. It was expected that the present polymers would be effectively transferred into phagocytes by encapsulating in polysaccharide-coated liposomes and would show increased pharmaceutical activities similar to poly(maleic acid-a/l-2-cyclohexyl-l, 3-dioxap-5-ene) (MA-CDA) [68]. The activation of human neutrophils by poly(VAd) was evaluated by monitoring the in vitro superoxide anion production from activated human neutrophils. Shown in Table 15 is the superoxide liberated from human neutrophils (1 x 106 cells/ml) activated by poly(VAd) (0.5 mg/ml) as a function of time. Poly(VAd) encapsulated in mannan derivative-coated liposomes showed a... 

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