Divinyl Ether-Maleic Anhydride (Pyran) Copolymer used to demonstrate the Effect of Molecular Weight on Biological Activity

Breslow, David S.; Edwards, E. I.; Newburg, Norman R.

doi:10.1038/246160a0

Cited by 69 publications

(12 citation statements)

References 19 publications

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“…1) which, in aqueous solution, hydrolyzes to its corresponding polyearboxylic acid. The highly negatively charged pyran molecule is thought to simulate the nucleic acid phosphodiester backbone and has an approximate molecular weight of 17,000 (15).…”

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confidence: 99%

Affinity chromatography of viral DNA polymerases on pyran-sepharose.

Chirikjian¹,

Rye²,

Papas³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Pyran covaiently linked to cyanogen bromide-activated Sepharose has been shown to be an effective affinity matrix for several viral DNA polymerases. Differential salt elution of viral compared with cellular polymerases, as well as substrate elution, suggests the affinity nature for the matrix. Unlike some other affinity systems described, pyran-Sepharose is totally resistant to nuclease digestion and is stable at 4°for several months. DNA polymerases isolated from several viruses by detergent treatment were recovered in good yield. Analysis of iodinated proteins by sodium dodecyl sulfate-gel electro-.phoresis revealed that the DNA polymerase of avian myeloblastosis virus found in crude preparations. of the virus could be purified nearly to homogeneity by a single passage through the column. These results suggest that pyran-Sepharose is an effective affinity column that is potentially adaptable as part of a general purification procedure for viral DNA polymerases.

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confidence: 99%

Affinity chromatography of viral DNA polymerases on pyran-sepharose.

Chirikjian¹,

Rye²,

Papas³

1975

Proc. Natl. Acad. Sci. U.S.A.

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“…These actions, like those of the polynucleotides, probably depend on molecular weight, with larger molecular weight fractions being the more toxic. Pyran and polynucleotides are both toxic to the liver, as seen in central necrosis in dogs, and interference with drug metabolizing enzymes [80, 81, 94, 981. Anemia as well as leukopenia is characteristic of pyran's effect in mouse toxicology studies [12,13,261. This is an effect that relates to molecular weight.…”

Section: Pyran -Discussionmentioning

confidence: 99%

The biologic activity of polyanions: Past history and new prospectives

Regelson

1979

J. polym. sci., C Polym. symp.

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SYNOPSISThe toxicology of synthetic polyanions relates to molecular weight. This developed from experience with pyran copolymer (divinyl ether maleic anhydride copolymer), which was tested clinically as an antitumor agent and found to be too toxic for continued clinical trial. Synthetic polyanions of low molecular weight are potent stimuli to macrophage phagocytic function and possess antitumor activity. Increased host resistance to pathogens including bacteria, fungi, viruses, and trypanosomes is seen. In contrast to lower-molecular-weight fractions, higher-molecular-weight samples inhibit macrophage function, and apparently increased molecular weight > 15,000 is necessary for antiviral and immunologic stimulating capacity. One possible mechanism for the action of polyanions may relate to redistribution of calcium ions within the cell and increasing cyclic GMP activity. This is a redefinition for the role of polyanions in sol -gel alteration in cytoplasm. The killing effect of the polyanion-activated macrophage on tumor cells resembles that of the polyanion on the nucleus. Polyanions may be potent controllers of the stability of DNA within the nucleus and can act to derepress cells to turn on protein synthesis or, alternatively, inhibit enzymes involved in virus synthesis and control of RNA or DNA polymerase. Thus, they are cogent tools in an understanding of the physiology of nuclear interaction. Biological use for these agents can be developed not only in clinical approaches to inhibition of tumor or viral infection, but to eliminate plutonium, and provide selective enzyme inhibition and protein interaction which allows for isolation, neutralization, and characterization of blood and tissue protein and glycoprotein fractions vital for a wide range of pathophysiology.(1,000,ooO M.W.) Sulf. Chitoran Sulf. Pectic Acid AmidsSulf. Oxid. Cellulose Hydroxornic Acid Laminorin Sulfate aAll animals showed 10% body weight loss. Legend: +, % inhibition 50% or greater; (+), 30-49%. b leukemia [48, 59-621, C3H mammary tumor transplants [62], methylcholanthrene derived transplants [63], and dimethylbenzanthracene (DMBA) induced tumors [64], the LSTRA sarcoma [58], Madison lung carcinoma [65] and prostatic adenocarcinoma in the rat [66], and the M109 lung carcinoma and colon tumor [67]. Pyran prevents polyoma induced tumors and Rauscher leukemia in thymectomized mice [57]. Pyran induces interferon in both humans and mice [16 -18, 52, 681, but antitumor and antiviral activity do not correlate with interferon induction [25, 54, 691. Pyran can both stimulate and inhibit host immune response [l, 2, 25, 70 -761 and alter in vitro lymphoblastic response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) [70 -741. Pyran inhibits the early cation-dependent steps of complement activity (G. S. White, personal communication, 1976) [77, 781, but can activate the C3 bypass. Pyran can prevent adjuvant induced arthritis [76], and its effects on skin graft survival are controversial. Toxicologically, the clinically tested pyran fraction...

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“…After 210 days strength decreased only in the case of polyamide fibres. Valuable experience was provided by the investigation of Dacron vascular prostheses removed from the patients after [5][6][7][8][9][10][11][12][13][14][15] years. Degradation changes were observed, especially in domains where the crystalline structure of the fibre was perturbed by mechanical effects due to shaping.…”

Section: B) Mutual Interaction Between Soluble Compounds Of Naturalmentioning

confidence: 99%