Basic Copolymer Research Articles

In vitro adsorption of bile salts by colestipol hydrochloride.

The acid-base titration of colestipol hydrochloride exhibits no sharp inflection points, indicating a weakly basic anion-exchange copolymer. The swelling of colestipol hydrochloride in water and the adsorption of cholate anion are inversely related to pH and are, therefore, related to the ionization state of the copolymer. The Langmuir adsorption parameters at pH 7.5 and 37 degrees C are similar for cholate, glycocholate, and taurocholate anions. Adsorption capacity was not related to particle size and exceeded the adsorptive capacity of the external surface by three orders of magnitude. Therefore, it is believed that the swelling of colestipol hydrochloride makes extensive internal surface area available for adsorption of bile salts. The rate of adsorption depends on the concentration of sodium cholate to which the colestipol hydrochloride is exposed. Adsorption was complete within 5 min when the concentration was below the adsorptive capacity. In contrast, adsorption at levels of sodium cholate at or above the adsorptive capacity was not complete within a 3-hr test period.

Viscometric study of dilute solutions of polymer-polymer mixtures. Temperature and composition effects

Viscometric interaction parameters between pairs of homopolymers or an acidic and a basic copolymer in dioxane were determined by two procedures: (a) determination of the intrinsic viscosity of polymer (A) in dilute dioxane solutions of polymer (B) at 30°; (b) determination of the Huggins constants for 1:1 mixtures of polymers at 50°. The Δb 23 values obtained by these methods were different but positive and they increased from the most incompatible to the completely compatible system. Non-linear relations were found for the Huggins constant vs temperature and the intrinsic viscosity vs composition.

Immobilization of horse liver alcohol dehydrogenase on copolymers of glycidyl methacrylate and ethylene dimethacrylate

Alcohol dehydrogenase has been immobilized to the basic copolymer and its several derivatives using various techniques. Enzyme coupling to the supports with amino groups by means of glutaraldehyde was found the most suitable. Activity of alcohol dehydrogenase coupled to these amino supports was comparable to that of the enzyme bound to Sepharose. Thermal and pH stability of alcohol dehydrogenase increased essentially upon immobilization. Kinetic properties of the immobilized enzyme differed from those of free alcohol dehydrogenase, pH optimum shifted to alkaline range, and apparent Michaelis constants for substrates and coenzymes increased. Curvatures observed in Lineweaver-Burk plots for coenzymes suggest an involvement of diffusion effects in the reaction catalyzed by alcohol dehydrogenase linked to these polymers.

Interaction of the basic copolymer — poly(ornithine, leucine) with normal and transformed cells

Interaction of the basic copolymer — poly(ornithine, leucine) with normal and transformed cells

Suppression of experimental allergic encephalomyelitis in rhesus monkeys by a synthetic basic copolymer

Experiments with rhesus monkeys demonstrate that a random basic copolymer of amino acids, denoted Cop 1, suppresses experimental allergic encephalomyelitis (EAE) when administered to the animals after clinical symptoms have already appeared. Fifteen daily injection of this material caused reversal of disease symptoms in the two treated monkeys, one of which suffered relapse 38 days later. When no treatment was given, the control monkeys deteriorated rapidly and died within a short time after onset of symptoms. Histological tests indicate EAE lesions in the brains of all monkeys except the monkey saved by Cop 1.

Action of a basic copolymer of ornithine and leucine on cells of Staphylococcus aureus.

A basic, random copolymer of l-ornithine and l-leucine (OL; molar ratios 1:1) was bactericidal to a sensitive (S) strain of Staphylococcus aureus at low concentration. Resistant cells (R) were selected from the culture medium and, after serial transfers to solutions containing increasing amounts of the polymer, grew well in the presence of very high concentrations of it (1,000 mug/ml). S cells bound much more OL than did R cells, but no difference in binding was shown between separated cell walls or cell membranes of S and R. The binding of OL and sensitivity to it were not dependent on the teichoic acid-content of the cells. Bound OL was only partially removed from the cells by a variety of reagents, such as sodium dodecyl sulfate, Triton X-100, dilute trichloroacetic acid, and Ba(OH)(2), and the extent of removal was similar for R and S cells.

Suppression by several synthetic polypeptides of experimental allergic encephalomyelitis induced in guinea pigs and rabbits with bovine and human basic encephalitogen.

AbstractThe basic copolymer of alanine, glutamic acid, lysine and tyrosine, denoted Cop 1, is an efficient suppressor of experimental allergic encephalomyelitis (EAE) induced with the bovine basic encephalitogen in guinea pigs and rabbits. The suppression was very effective also when the experimental disease was induced with the basic protein from human source. Two related polymers, one in which glutamic acid was replaced with aspartic acid, and one devoid of tyrosine, were less effective in the suppression of the experimentally induced disease.The route of administration of Cop 1 plays an important role in its suppressive effectiveness, with intravenous injections being the most efficient. The injection schedule and dose of injection are also of great importance; thus, repeated doses of Cop 1 starting five days after the administration of the basic protein are suppressive, whereas a single dose of 5 mg given 72 h after challenging with the basic protein does not suppress EAE. Cop 1 is not a nonspecific immunosuppressant, as it does not affect the immune response towards a variety of antigens, including the rejection of a skin graft.When EAE was induced with the human encephalitogen, the histological changes observed included demyelination and fibrosis in the guinea pig brain.

Cellular aspects of the inverse relationship between the net charge of immunogens of antibodies elicited.

The results reported establish a cellular basis for the inverse relationship between the net electrical charge of immunogens and of the antibodies provoked by them. Glass bead columns were used to reduce the number of immunocompetent spleen cells preferentially reactive with more acidic immunogens. After a single immunization, titers of antibodies to an acidic dinitrophenylated copolymer of tyrosine, glutamic acid, and lysine (DNP-901) elicited in recipient mice by filtered spleen cells were significantly lower than those generated by unfiltered cells. After secondary stimulation, the major portion of the antibodies provoked by the acidic antigen was found in the more acidic fraction eluted from DEAE-Sephadex, in contrast to the more basic antibodies, of the same specificity, generated by unfiltered spleen cells. Results obtained by transplanting a limiting number of spleen cells indicate a depletion in the number of precursor cells reactive with dinitrophenyl on DNP-901 after glass bead chromatography, whereas there was no change in the response to dinitrophenyl on a basic copolymer, DNP-912, containing the same amino acids in different molar ratios.

Specific aggregation of SV40-transformed cells by ornithine, leucine copolymers.

A basic copolymer of ornithine and leucine (1:1) was shown to rapidly agglutinate, in the absence of serum, normal cells and cells transformed by viral and nonviral carcinogens. This agglutination was inhibited by addition of serum. In presence of serum, the same copolymer and those of ornithine and valine (1:1) and arginine and leucine (1:1), produced a specific aggregation of simian virus 40 (SV40)-transformed cells cultured for about 24 hr after addition of the peptide. The rapid agglutination and SV40-specific aggregation could not be inhibited by a variety of individual amino acids or carbohydrates. The specific aggregation could be detected in mixtures of SV40-transformed and other cells, and it was not prevented by x-irradiating the cells with 4000 R. Aggregation of the SV40-transformed cells was inhibited by acidic polyamino acids provided these were added not later than about 5 hr after addition of the basic copolymer. The results indicate that the basic copolymer, in the presence of serum, produces a change in SV40-transformed cells, presumably in the surface membrane, that causes the cells to aggregate. In addition to the aggregation of cells transformed by SV40, cells transformed by adenovirus 12, which did not contain detectable SV40-specific nuclear tumor (T) antigen, were also aggregated by the basic copolymer in the presence of serum. This indicates that the ornithine, leucine copolymer is able to detect an SV40-like change in the surface membrane of cells transformed by adenovirus 12.

Polymer association. I. Osmotic pressure of solutions of mixed acidic and basic polymers

AbstractMethyl methacrylate was copolymerized with small amounts of methacrylic acid or dimethylaminoethyl methacrylate. The molecular weight of the basic copolymer calculated from osmotic pressure data in butanone and benzene gave consistent results. The molecular weight of the acidic copolymer was obtained from osmotic pressures of pyridine solutions, but in butanone and particularly in benzene strong molecular association was observed. Osmotic pressures of mixtures of the two copolymers in butanone at 30.2 and 50.1 and in benzene at 49.7°C. were determined. The reduced osmotic pressure plots were linear but indicated the persistence of molecular associations to the highest dilutions at which osmotic pressures could be measured. A thermodynamic analysis of the data showed that under certain conditions the activity of one or the other polymer component decreases with increasing concentration of the mixture.