Synthetic double-helical complexes

Theoretically, it may be possible to artificially increase the production of interferon by the action of an inducer. Synthetic double-stranded ribonucleotide polymers, in particular the double-helical complex of polyinosinic acid with poly-cytidylic acid RNA (poly IC) are used in this way These agents activate the synthesis of interferon. They increase the resistance to viruses of cells m culture, and promote recovery in rabbits suffering from herpetic eye infection. This type of activity is an important prospect in the field of antiviral therapy. 

The anti-poly I poly C antibodies react not only with RNA of reovirus but also, though to a lesser degree, with RNA extracted from mammalian cells (Fig. 4). Comparison of the efficiency of inhibition of the cross-reaction with mammahan RNA by RNA of reovirus, by double-helical complexes of synthetic polynucleotides and by single-stranded polynucleotides, has shown that the antibodies anti-poly I poly C react especially with double-stranded conformational determinants of the RNA. None of the single-stranded polynucleotides is capable of totally inhibiting the reaction with RNA whatever... 

Differences in the capacity of inhibition by polynucleotides not involved in complementary hydrogen bonds and by double-helical complexes of synthetic polyribonucleotides, or double-stranded viral RNA allow the conclusion that it is above all the regions of associated base pairs which are recognized in the RNA by anti-poly I poly C antibodies. Such complementary double-stranded helical regions have been described especially in tRNA but they have also been shown to exist in ribosomal RNA. These two kinds of RNA were therefore isolated and studied separately. Although both fractions precipitate anti-poly I poly C antibodies, their reactivity is nevertheless very different and rRNA precipitates eight times as much antibody as tRNA. Since tRNA possesses an important tertiary structure, this low reactivity could be explained by the non-accessibility of antigenic sites. 

It is essentially the cross-reactions with another double-helical complex, poly A poly U, which have been studied with immune sera of mice and hamsters. These cross-reactions have been observed very frequently with immune sera of RAP mice and B/W mice and to a lesser degree with the sera of hamsters poly A poly U is the best inhibitor of the reaction between anti-poly I poly C of mice and the homologous antigen (Lacour et al., 1971 Steinberg et al., 1971). The role of the bases in this immunoreaction does not appear to be essential. It is probable that, as in rabbit, these antibodies recognize double-helical structures. While there is similarity in the reactions of the sera of the three species with synthetic polynucleotide double-helical complexes, the cross-reactions of the anti-poly I poly C antibodies with nucleic acids are very different in the rabbit, the mouse, and the hamster (Table 4). 

A completely different synthetic strategy can be used to prepare multiblock copolymers. For instance, a copolymer containing an oligoether and two complex-forming blocks gives a multiblock copolymer with double helical supramolecular segments when its solution in chloroform is added with Cu(I)-trifluoromethanesulfonate (Schemes 50 and 51) [66,67]. 

Since several synthetic polymers also develop a blue color upon reaction with iodine, it is likely that they have a helical structure similar to that of amylose. Therefore it is probable that the aforementioned complexes of synthetic polymers with starch can exist in the form of a double helix. 

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