Polynucleotides, synthetic, conformation

Most native DNAs and certain synthetic polynucleotides are able to undergo a B A conformational transition. In films and fibers, this transition may be induced by decreasing the relative humidity to which the sample is exposed. This is demonstrated by the Raman spectra of fibers (Erfurth et al., 1975 Martin and Wartell, 1982 Prescott et al., 1984) and by the IR spectra of films (Pilet and Brahms, 1973 Taillandier et al., 1985) made of native DNAs. In the case of polynucleotides, the decrease of relative humidity affords different results, depending on the sequence of the polymer. Thus, poly d(A-T) and poly d(A-C). poly d(G-T) - double stranded DNA with one strand adenine and cytosine and in the other guanine and thymine - show a classical B A transition (IR Brahms et al 1976 Taillandier et al., 1984a Adam et al., 1987. Raman Thomas and Benevides, 1985 Jenkins et al., 1986). 

The strong interactions between certain bivalent cations and the highly ordered polynucleotides such as DNA, certain synthetic duplex homo- and heteropolymers, and s-RNA have been the subject of much current interest. With this idea in mind, it is interesting to note that the steroidal diamine cyclobuxine-D (242) was shown to exert a profound effect on the stability of helical polynucleotides (DNA, s-RNA, and dAT dAT). The effect is biphasic in the sense that at low concentrations of the agent there is stabilisation of the native conformation, while at higher concentrations there is stabilisation of the denatured conformation. 

Since RNA double helices and most RNA/DNA hybrids have only been observed in conformations similar to the A-form [14-24] whereas studies of the DNA conformation in cells such as salmon sperm have revealed that the resting state of DNA appears to be the B-form [25], it is natural to speculate that the B-form is adopted for DNA replication whereas the A-form is adopted for transcription. Similar considerations apply in the case of synthetic polynucleotides a polynucleotide with a highly repetitive base sequence can be found in the S form under conditions in which a natural DNA with essentially random base sequence would be found in the B form. Highly repetitive sequences flanked on both sides by random sequences are known to exist in natural DNAs and so it is possible that under some ionic conditions the repetitive and random sequences would have different conformations. The potential to exploit such structural differences in control processes mediated by specific DNA-protein recognition mechanisms is clear. Although these speculations have not been confirmed, the fact that conformational transitions may be implicated in such fundamental biological processes is powerful justification for extensive study of the stereochemical pathways of these transitions and the factors which promote and control them. 

Hashizume H, Imahori K (1967) Circular dichroism and conformation of natural and synthetic polynucleotides. J Biochem (Tokyo) 61 738-749... 

Hilleman and his co-workers have demonstrated interferon production following the administration of reovirus RNA or the replicative form of RNA isolated from E. coli infected with MS2 coliphage. These BNAs are effective in inducing resistance to virus infection m vitro and vivo. The induction of interferon and the broad-spectrum protection against viral infection conferred by double-stranded RNA suggested the use of synthetic polynucleotides, including polyriboinosinic-polyribocytidilic acid, which possess a double-stranded conformation. Chemically modified RNA may also induce the production of interferon. ... 

We have been interested in the conformations of simple sequence synthetic polynucleotides. Figure 7 shows a comparison between calculated and observed CD of four RNA double strands [19]. The agreement is not very good but poly rA poly rlJ and poly rG poly rC give reasonable agreement. We conclude that these two polynucleotides have RNA geometry this conformation is similar to A-form DNA. However, the alternating sequences... 

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... 

Studies of the specificities of experimentally induced antipolynucleotide antibodies have yielded some information on the antigenic determinants which could exist in a molecule of nucleic acid. Like the antibodies to proteins or synthetic polypeptides, antibodies to polynucleotides can be directed against different antigenic determinants derived from sequential regions as well as conformational factors in the molecule. Since antibodies in which the specificity is associated with the heterocyclic bases are obtained by use of single-stranded polynucleotides or certain components of nucleic acids it is thus evident that the bases themselves can be included among the antigenic determinants of polynucleotides. 

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 have seen in various sections of this article that anti-RNA antibodies induced by immunization with ribosomes and the antibodies to pol3uibo-nucleotide complexes — MBSA have made possible a more direct approach to the study of the conformation and structure of synthetic polynucleotides and both viral and non-viral natural ribonucleic acids. 

As was seen in Section III,C,1 the broad P-NMR lines of the B form of natural DNA suggested that the pho hodiesters have a considerable dispersion in their orientation relative to the helical axis. If such a variation of the backbone conformation was induced by difference in base sequence, synthetic polynucleotide with a known sequence would emphasize a unique... 

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