Polycytidylic acid poly

Interferon is a low molecular weight protein, produced by vims-infected cells, that itself induces the formation of a second protein inhibiting the transcriphon of viral mRNA. Interferon is produced by the host cell in response to the vims particle, the viral nucleic and non-viral agents, including synthetic polynucleides such as polyinosinic acid polycytidylic acid (poly I C). There are two types of interferon. 

Similar experiments were carried out with different synthetic polyribonucleotides. It was found, for example, that polyadenylic acid (poly A) leads to the synthesis of polylysine, and that polycytidylic acid (poly C) leads to the synthesis of polyproline. By 1964, all 64 codons had been deciphered (Table 20.4). Nirenberg, R. W. Holley, and H. G. Khorana shared the 1968 Nobel Prize in Physiology or Medicine for their seminal work. 

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. 

A synthetic short double-stranded RNA such as Polyinosinic-polycytidylic acid (poly(I)-poly(C)) is widely used as a inducer in interferon production. The presence of DEAE-Dextran in the reaction medium increases the uptake of poly(I)-poly(C) by the cells and also makes the polynucleotide less susceptible to degradation from RNase. In addition, the... 

The ability of certain polymer sequences to spontaneously form secondary structures influences their migration through nanopores. As examples, let us consider the translocation events of single-stranded polynucleotides through a-hemolysin protein pore in the electrophysiology experiments. The event plots of translocation (every data point in the plot referring to the dwell time and the ionic current of a particular blockade event) for polycytidylic acid (poly C) and polydeoxycytidylic acid (poly dC) are compared in Figure 11.3a,... 

Abbreviations DNA deoxyribonucleic acid RNA ribonucleic acid rRNA ribosomal RNA tRNA transfer RNA. A adenine U uracil G guanine C cytosine, poly A polyadenylic acid poly U polyuridylic acid poly C polycytidylic acid poly I poly-inosinic acid poly G polyguanylic acid. The letters r and d refer to the ribose or deoxy-ribose series. Complexes between the polynucleotides are written as follows polyG poly C double-stranded helical complex of poly G and poly C 2 poly G poly C, triple-stranded complex. BSA bovine serum albumin MBSA methylated bovine serum albumin. N nitrogen. AMV Avian myeloblastosis virus NDV Newcastle disease virus. SLE systemic lupus erythematosus. 

Polyinosinic polycytidylic acid (Poly I C) - a TLR3 agonist... 

Lactide/glycoUde polymers have been investigated for delivery of several other macromolecules. Synthetic double-stranded RNA, poly-isosinic acid/polycytidylic acid, a potent inducer of interferon, was formulated in a 53 47 copolymer of DL-lactide-co-glycoUde. The microspheres were evaluated in mice challenged with Right Valley fever virus. More than 16 days protection was afforded versus only 3 days for controls (137). 

C. Oligo- and Poly-nucleotides.—The stepwise enzymatic synthesis of internucleotide bonds has been reviewed. A number of polynucleotides containing modified bases have been synthesised " in the past year from nucleoside triphosphates with the aid of a polymerase enzyme, and the enzymatic synthesis of oligodeoxyribonucleotides using terminal deoxynucleotidyl transferase has been studied. Primer-independent polynucleotide phosphorylase from Micrococcus luteus has been attached to cellulose after the latter has been activated with cyanogen bromide. The preparation of insolubilized enzyme has enabled large quantities of synthetic polynucleotides to be made. The soluble enzyme has been used to prepare various modified polycytidylic acids. ... 

Fig. 23. Effects of thiolated polycytidylic acid (MPC) and unmodified polycytidylic acid (PC) on the DNA polymerase activities from MSV (Moloney) in the presence of poly rA-(dT)j4 ( ------ ) and poly (dA-dT) (O------O) as templates...

Fig. 23 shows the effects of 5-mercapto-(9.5%)-polycytidylic acid (MPC) and modified polycytidylic acid (PC), respectively, on the incorporation of 3H—TMP into DNA by the DNA-polymerses of the MSV-M, in the presence of either poly.(dA-dT) or poly rA (dT)i4 as the template. The results obtained with the same pair of modified and unmodified polycytidylic acid samples in... 

Giri SN, Hyde DM. 1988. Ameliorating effect of an interferon inducer poly-inosinic-polycytidylic acid on bleomycin-induced lung fibrosis in hamsters morphologic and biochemical evidence. Am. J. Pathol. 133 525-36... 

The inducible production of interleukin-6 and interferon-y by alveolar macrophages lavaged from Fischer 344 rats exposed to ammonium metavanadate (2 mg V/m ) for 8 h/d for 4 d, followed, 24 h later by intratracheal instillation of 0.15 mg polyin-osinic polycytidylic acid in 100 il saline, within 24 h increased 11-fold and 20-fold, respectively, vs. 30-fold and 7-fold, respectively, in air control rats (Cohen et al. 1997). At 24 h following poly I C instillation, there were no significant host exposure dependent differences in either spontaneous of opsonized zymosan-stimulated O2 " formation. At 48 h a time post poly HC-dependent effect upon opsonized zymosan-stimulated pulmonary alveolar macrophage 02 production was evident this effect was greater in macrophages from rats exposed to V prior to poly I C instillation than in similarly instilled air control animals. 

Talal, N., Steinberg, A. D., Daley, G. G. Inhibition of antibodies binding poly-inosinic polycytidylic acid in human and mouse lupus sera by viral and S mthetic ribonucleic acids. J. din. Invest. 50, 1248-1252 (1971). 

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