Synthetic polynucleotide complexes

Synthetic polynucleotide complexes have been shown to be effective immune response modulators in animals and man (Braun et al. 1971, Johnson 1979). The polynucleotides are formed foUowing the action of an enzyme, polynucleotide phosphor-ylase on the synthetic mononucleotide diphosphates. Complexing takes place following the mixing of polymers composed of opposite base pairs. Two have been utilised, polyinosinic acid complexed with polycytidylic acid (poly I poly C) and polyad-enylic acid complexed with polyuridylic acid (poly A poly U). The single strands mononucleotides are ineffective. 

Field, A.K., Tytell, A.A., Lampson, G.P., and Hilleman, M.R., 1967, Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes, Proc Natl Acad Sci USA,... 

Like double-stranded DNA, synthetic polynucleotide complexes containing complementary bases show cooperative melting curves, i.e., the property studied (UV absorption, optical activity, viscosity, etc.) shows a sharp transition at a specific temperature. This Tm depends on ionic strength and, to a certain degree, on pH. If the temperature is increased above the Tm, however, a further continuous variation in the property studied will be observed. It is only in recent years that an understanding of such noncooperative phenomena is emerging. Here the studies of oligomers by CD and NMR were of critical importance. 

The existence of conformational determinants has been clearly demonstrated through the use of synthetic polynucleotides in double-hehcal structures and in triple-stranded complexes. It has also been shown that the specificity of antibodies is determined by the macromolecular conformation of the immunogen. Thus single-stranded polynucleotides induce formation of antibodies specific for the single-strand, while double-stranded hehcal complexes of polynucleotides induce antibodies specific for these structures, and antibodies specific for triple-strand structures are induced by the triple-stranded polynucleotide complexes. 

We shall conclude this section by a comparison of Equations (30) and (34) with published data. Using a dye indicator for Mg , Krakauer [17] measured a quantity 6 which is identical to the l.h.s. of these equations. In Figure 1 is portrayed his data for the synthetic polynucleotide complex Poly (A+2U), characterized [18] by the... 

This contribution complements an earlier review (11) which summarized our NMR research on synthetic DNA s and RNA s with alternating inosine-cytidine and guanosine-cytidine polynucleotides and the structure and dynamics of ethidium-nucleic acid complexes. 

Because of the complex behaviour to be expected for natural nucleic acids, it is only natural that considerable effort has been devoted to studies of the electrochemical properties of their monomeric units, and defined analogues of these, as well as of synthetic oligo- and polynucleotides. A variety of techniques has been applied for this purpose, and some of the details and findings are covered in several reviews 19 24). Most investigations have dealt with electroreduction processes 15 20,24,25). Only relatively recently has attention been directed to possible electrooxidation of nucleic acids and their constituents with the aid of the graphite electrode which, in comparison with the mercury electrode, possesses a much greater accessible range of positive potentials 26 29). 

The photochemical response of bacterial DNA and of synthetic polynucleotides to UV, and of the influence thereon of Hg " and Ag have been examined [119, 120], The photochemistry of DNA is altered greatly when these metals are bound, but in different ways. Hg " complexed with bacterial DNA greatly reduces the rate of thymine dimerization, whereas Ag" binding to DNA greatly enhances dimerization. Consequently, biological inactivation is increased in the presence of Ag but reduced with Hg ". 

A second structural requirement for the interferon-inducing capacity (antiviral activity) of synthetic polynucleotides is a stable, highly ordered secondary, hence double-stranded structure based on complementary base-pairing. The stability of the complex is reflected in its Tm (thermal stability) value. From a comparative study of different double-stranded RNA duplexes, De Clercq and Merigan61-1 and De Clercq et al. 53-) concluded that a Tm value higher than 60 °C (calculated for 0.15M Na+) was needed for full expression of antiviral activity. Since thermal stability represents a valuable measure of the overall stability of double-stranded RNAs116 double-stranded RNAs with Tm values higher than 60 °C may also be considered to be the most stable ones at 37 °C. 

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