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At least 721 records · Page 40Linked to original sources
PubMed1986

Interaction of polystyrene/poly(gamma-benzyl L-glutamate) and poly(methyl methacrylate)/poly(gamma-benzyl L-glutamate) block copolymers with plasma proteins and platelets.

A-B-type block copolymers, consisting of polystyrene (PST) or poly(methyl methacrylate) (PMMA) forming segment (A) and poly(gamma-benzyl L-glutamate) (P[Glu(OBzl)]) segment (B), were synthesized and the thrombus formation on these block copolymer films was investigated in relation to the adsorption of plasma proteins and the activation of platelets. The relative amount of thrombus formation was higher on homopolymers than on block copolymers. The amount of thrombus formation became less, with decreasing content of P[Glu(OBzl)] in the PST block copolymers and with increasing content of P[Glu(OBzl)] in the PMMA block copolymers. Adsorption of bovine serum albumin(BSA), bovine gamma-globulin (B gamma G) and bovine plasma fibrinogen(BPF) onto polymer films was also investigated. More proteins were adsorbed and denatured when adsorbed onto PST and PMMA than onto block copolymers. With increasing content of P[Glu(OBzl)] in the PST block copolymers, the degree of denaturation of adsorbed proteins increased, while the amount of protein adsorption was unaffected. Conversely, with increasing content of P[Glu(OBzl)] in the PMMA block copolymers, the degree of denaturation of adsorbed proteins decreased, while similarly the amount of protein adsorption was unaffected. Adhesion of platelets from platelet suspension (WP) to polymer films coated with one of the plasma proteins showed that the activation of adhered platelets was suppressed when there was a lower degree of denaturation of coated proteins. In the same experiments using platelet-rich plasma(PRP), neither the number of platelets adhered nor the degree of activation of the adhered platelets was correlated with the composition of the polymer films.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1988

Gas permeability of the film of block and graft copolymers of polydimethylsiloxane and poly(gamma-benzyl L-glutamate).

A-B-A type block copolymers of poly(gamma-benzyl L-glutamate) (PBLG, A segment) and polydimethylsiloxane (PDMS, B segment) and PDMS (trunk)-PBLG (branch) graft copolymers were synthesized, and the permeation of oxygen in water and the permeation of oxygen and carbon dioxide in the dry state were investigated. The gas permeation coefficient (P) increased with increasing content of PDMS. However, PCO2/PO2 values of copolymer films were in the range 6-9, i.e. larger than 5.4 for PDMS film. The oxygen permeation in water suffered from the interfacial resistance, which was reduced by the hydrolysis of film surface. The Arrhenius plot of the gas permeation coefficient in the dry state of the block copolymer B showed a turning point at about 40 degrees C. This temperature is close to beta-peak temperature (39 degrees C) and may be ascribed to the molecular motion of the PBLG segment. Transmission electron microscopy showed that one of the block copolymer films (PDMS 46 mol%) appears to have PDMS segments dispersed in the PBLG matrix (island-in-sea structure) and one of the graft copolymer films (PDMS 58 mol%) appears to take a lamellar structure. The gas permeation across the graft copolymer film appears to occur through the continuous PDMS phase, leading to a near-negligible activation energy in this process.

Biocompatible Materials↗
PubMed1988

Adsorption of plasma proteins and platelet adhesion on to polydimethylsiloxane/poly(gamma-benzyl L-glutamate) block copolymer films.

A-B-A-type block copolymers of four different compositions were synthesized, in which A and B represent poly(gamma-benzyl L-glutamate) and polydimethylsiloxane segments, respectively. Among the block copolymers and their surface-modified derivatives, those containing 40-70 mol% polydimethylsiloxane and having water contact angles ranging from 50 degrees to 85 degrees were found not to induce conformational change of plasma proteins upon adsorption. It was also observed that the number of adhered platelets and the rate of serotonin release from adhered platelets increased when plasma proteins underwent conformational change upon adsorption. These experimental observations indicate that hydrophobic-hydrophilic block copolymers having a certain composition do not induce conformational change of plasma proteins upon adsorption and do not adhere to and activate platelets, thus leading to a suppression of thrombus formation.

Adsorption↗
PubMed1990

Enzymatic hydrolysis of copoly-(N-hydroxyalkyl L-glutamine/gamma-methyl L-glutamate) fibres.

Fibres from random copolypeptides consisting of N-hydroxyalkyl L-glutamine and gamma-methyl L-glutamate with different monomer ratios were prepared by aminoalcoholysis of a poly(gamma-methyl L-glutamate) fibre with 2-amino-1-ethanol or 5-amino-1-pentanol, both with 1,8-octamethylenediamine as cross-linking agent. The initial tensile properties as well as the in vitro hydrolysis of these hydrophilic fibres were highly dependent on the degree of swelling in phosphate buffer solution. The in vitro hydrolysis was carried out using pronase E as protease. The kinetic study on the weight loss of the fibre accompanying the enzymatic hydrolysis suggested that the degradation of these fibres proceeds gradually from the surface of the fibres into their core. Scanning electron microscopy also supported the surface, not bulk, hydrolysis. The weight loss of the fibres in the course of hydrolysis took place almost in parallel with the strength loss of the fibres.

Biodegradation, Environmental↗
PubMed1994

Preparation and properties of A-B-A type block copolymer membranes consisting of poly(N-hydroxypropyl-L-glutamine) as the A component and polyisoprene as the B component.

A-B-A type block copolymer (GIG(P)) membranes consisting of poly(N-hydroxypropyl-L-glutamine) (PHPG) as the A component and polyisoprene (PI) as the B component were prepared by carrying out aminoalcoholysis reaction with 3'-amino-1-propanol and a crosslinking reaction with 1,8-octamethylenediamine (OMDA) on membranes of the starting block copolymer (GIG) membranes consisting of poly(gamma-benzyl L-glutamate) (PBLG) and PI. It was shown that the effective crosslink density was proportional to the molar % of OMDA in the reaction mixture. The relation between their bulk structure and membrane properties was investigated, such as the swelling ratio q in a pseudo-extracellular fluid (PECF), tensile properties, and enzymatic degradation behaviour of the membranes in PECF. The tensile properties of the hydrophilic membranes were highly dependent on q in PECF, and on the hydrophobic portions in molecular chains, whose behaviour was typical of an elastomer. Biodegradation of samples in vitro by papain indicated that the rate of degradation was also highly dependent on q of membranes in PECF.

Biocompatible Materials↗
PubMed1995

Surface properties and biocompatibility of A-B-A type block copolymer membranes consisting of poly(gamma-benzyl-L-glutamate) as the A component and polyisoprene as the B component.

The surface characteristics of A-B-A type triblock copolymer (GIG) membranes consisting of alpha-helical poly (gamma-benzyl-L-glutamate) (PBLG) as the A component and polyisoprene (PI) as the B component were investigated by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The XPS measurements showed the copolymer composition of the outermost surface to be quite different from the bulk composition. Results of contact angle measurements indicated the existence of an interfacial region between the alpha-helical A component and the B component at the surfaces of the block copolymer membranes. Finally, the results of in vivo tests on tissue compatibility indicate that the GIG block copolymer membranes have good biocompatibility.

Animals↗
PubMed1991

Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.

The basis of intrinsic resistance of blasts from patients with acute non-lymphocytic leukemia (ANLL) to methotrexate was studied. MTX polyglutamate formation was measured in blast cells from 19 patients with ANLL and in 7 pediatric patients with acute lymphocytic leukemia (ALL), after in vitro incubation for 24 h with 3H-methotrexate. There was no significant differences seen in the total amount of MTX plus polyglutamates measured between ANLL and ALL blasts, indicating that transport defects do not account for intrinsic MTX resistance in ANLL. However, there were significant differences between the amounts of long chain MTX polyglutamates found in ANLL cells as compared to ALL cells. Most, but not all, ANLL blasts were unable to form long chain polyglutamates. In as much as the level of MTX polyglutamates found in blast cells after MTX administration allows for retention of this drug, this property may explain, at least in part, the refractoriness of most patients with ANLL to methotrexate.

Adolescent↗
PubMedDate not supplied

Enzyme studies of methotrexate-resistant human leukemic cell (K562) subclones.

Five methotrexate (MTX)-resistant K562 cell subclones (K562/MTX-1 approximately -5) were established and were examined for mechanisms of drug resistance. Impairment of MTX-polyglutamate formation, with membrane transport alteration, in the resistant cells was demonstrated in the previous studies (Koizumi, S. (1988) Jpn. J. Cancer Res. 79, 1230). Further analysis of sensitivity of the cells to trimetrexate (TMQ), which is not polyglutamated and does not require the reduced folate transporter, but is a potent inhibitor of human DHFR, revealed a modest decrease in sensitivity to TMQ (2.4- to 15-fold). Enzyme studies showed that the dihydrofolate reductase (DHFR) activities of these resistant subclones were very similar to that of the parent cells. The number of binding sites of these subclones for MTX calculated from Scatchard analysis was increased up to 7-fold in the K562/MTX-1 and -4 subclones and up to 3-fold in the other 3 subclones as compared to the parent cells. KD values of MTX for the DHFR in the K562/MTX-1 and -4 subclones also appeared to be altered relative to the parent cell line. Further, thymidylate synthase (TS) activity of the resistant subclones was reduced to 50% in K562/MTX-1 and -4 cells, and to 11-25% in the other subclones as compared to the parent cell line. These findings suggest that antifolate resistance in the newly established K562/MTX subclones in multifactorial with polyglutamation and transport defects accounting for the majority of resistance to MTX, and that alteration in the binding affinity of DHFR for MTX and diminished levels of TS may contribute to the 'residual' drug resistance to TMQ and have importance with respect to MTX.

Binding Sites↗
PubMed1982

On the mechanism of Clq binding to antibody-I. aggregation and/or distortion of IgG vs combining site-transmitted effects.

It was shown previously that in sheep calcium-dependent anti-GAT there is a subpopulation which reacts with and can be precipitated with poly G [Liberti (1975) Immunochemistry 12, 303-310]. This entire subpopulation was also found to react with the cross-reacting polypeptides GA and GT. Furthermore, from hydrogen exchange experiments, it was found that only the immunizing antigen GAT completely filled the combining sites of these antibodies whereas poly G was shown to occupy an average of 47% of all sites, and GA and GT, 75 and 85% respectively. Since precipitins formed with this subpopulation and each of these antigens should have reasonably similar densities and orientations of 'aggregated' IgG but differing combining sites occupancies, we have used this system to explore the relative role of Fc aggregation and/or IgG distortion vs combining site-transmitted effects on the binding of Clq to antibody. For two preparations of this subpopulation (one of high avidity, the other obtained via poly G-Sepharose and of lower avidity) there is only a 5% difference in the delta G (10.2-10.8 kcal/mole) of Clq-IgG interaction for a change in combining site occupancy of 47-100%. For the high-avidity preparation there is a correlation between delta G and degree of ligand occupancy of combining site. This could reflect combining site-transmitted effects or may be related to small differences in the molecular architecture of these precipitins. Clq saturation curves support the latter notion. In view of the very moderate effect of combining site filling (from 47 to 100%) on Clq-IgG interaction for the high-avidity preparation and the absence of any correlation for the lower-avidity preparation. It appears that an allosteric model for antibody initiation of complement is untenable. Unless combining site-originating contributions are completed when less than 50% of an antibody-binding site is occupied by ligand, it would seem that Clq binding to immune complexes must be governed either by enhanced interactions resulting from Fc clustering which occurs via antibody interactions with antigen or by distortion of the antibody molecular upon ligand binding or some combination thereof.

Allosteric Regulation↗
PubMed1987

Unusual "cytokine" activities of the random polymer (Glu60, Phe40) in murine immune systems.

When the random polymer (Glu, Phe)n was added to primary lymph node T cell cultures from mice immunized with (Glu, Lys, Ala) and other immunogens, significant inhibition of [3H]thymidine incorporation was noted. A similar addition of (Glu, Phe)n to murine T cell lines (Fathman) from the above reacting lymph nodes led to augmentation of maximal incorporation of [3H]thymidine. The importance of the antigen presenting cells in these phenomena and the possible role of IL-1 in these observations will be documented.

Animals↗
PubMed1990

Effect of polyanions and polycations on detyrosination of tubulin and microtubules at steady state.

Microtubule protein preparations purified from rat brain were used to study the effect of polycations and polyanions on the release of the COOH-terminal tyrosine of the alpha-chain of tubulin catalyzed by tubulin carboxypeptidase. (1) Most of the polycations and polyanions tested, independently of the ionogenic group, inhibited the reaction in a concentration-dependent fashion. Under steady-state conditions, detyrosination of the microtubule pool was inhibited to the same degree as occurred with the non-assembled tubulin pool, except in the case of chondroitin sulphate. This compound inhibited detyrosination of the non-assembled tubulin pool, but not that of microtubules. (2) Heparin, the most potent inhibitor tested, produced the dissociation of the carboxypeptidase from microtubules. Many, but not all, of the other microtubule-associated polypeptides were also dissociated by heparin. (3) Polylysine counteracted the inhibitory and dissociating effects of heparin. (4) Heparin protected tubulin carboxypeptidase against inactivation. Our results and previous reports describing, in nervous tissue, the presence of proteoglycans, RNA and basic proteins that inhibit detyrosination, suggest that tubulin carboxypeptidase might be physiologically modulated by electrically charged macromolecules.

Animals↗
PubMed1987

Protein kinase C phosphorylation of protamine is Ca2+ independent, but the addition of DNA renders it Ca2+ dependent.

Protamine is a unique substrate of protein kinase C for its Ca2+-independent phosphorylation. The interaction between protein kinase C and protamine and the effect of DNA on the interaction was studied. Protein kinase C was retained in a protamine-immobilized Sepharose 4B column, even in the absence of Ca2+ and was eluted with ammonium sulfate or L-arginine. The eluted enzyme was fully activated by phosphatidylserine alone, when protamine was used as substrate. When DNA was included in the assay system, the activity elicited by phosphatidylserine alone was inhibited. The DNA effect on the activity in the presence of both Ca2+ and phosphatidylserine was much lower than on the activity elicited by phosphatidylserine alone, thereby demonstrating the Ca2+ sensitivity of protamine phosphorylation.

Animals↗
PubMed1986

Effects of pressure and potassium chloride on the aggregation of poly(gamma-benzyl-L-glutamate) in liposomal bilayers.

Fluorescence depolarization studies were made on dimyristoylphosphatidylcholine liposomes containing four kinds of dansylated poly(gamma-benzyl-L-glutamate) with different degrees of polymerization or hydrocarbon chain lengths under high pressure at up to 981 bar (1 bar = 10 MPa). Potassium chloride promoted the aggregation of the synthetic peptides in liposomal bilayers at both atmospheric and high pressure. The chain lengths of the hydrocarbons of the peptides had more influence than their degrees of polymerization on aggregation.

Dimyristoylphosphatidylcholine↗
PubMed1987

Hydrogen bonds between protein side chains and phosphates and their role in biological calcification.

Poly(L-histidine)-phosphate (H2PO4-, HPO4(2-)) and poly(L-glutamate)-phosphate systems (residue/phosphate, 1:1) in the presence of Ca2+ are studied by infrared spectroscopy. In the poly(L-histidine)-phosphate systems N...HOP in equilibrium NH+...O-P hydrogen bonds are formed where most phosphate protons are found at the histidine ring. With an increase in the degree of hydration the proportion of the proton limiting structure NH+...O-P increases. In the poly(L-glutamate)-dihydrogen phosphate system most phosphate protons are found at the carboxylate groups. Different behavior is observed for poly(L-glutamate)-hydrogen phosphate mixtures, where the residence time of the phosphate proton at the hydrogen acceptor carboxylate group is very short. This residence time increases, however, with increasing humidity. All these results support the triphasic theory of biological calcification involving a tripartite protein-calcium-phosphate complex where these hydrogen bonds can be present. The behavior of these hydrogen bonds can also explain the formation of a nidus of calcium phosphate salts in calcium oxalate-containing urinary calculi.

Animals↗
PubMed1980

Mechanism of activation of cyclic GMP-dependent protein kinase from rat liver by multiple modulators.

A number of polyanionic compounds, including DNA, RNA and polyglutamate, were shown to exhibit protein kinase stimulatory modulator activity as they were required for cyclic GMP to stimulate the phosphorylation of various cationic substrates by rat liver cyclic GMP-dependent protein kinase. Anionic proteins (casein, phosvitin) were phosphorylated poorly by the enzyme and their phosphorylation was not stimulated by the stimulatory modulators. Studies of the mechanism of action suggest that the modulators interact directly with the substrates to form a complex which is a better substrate than free histone. The observed effect of modulator is complex as it depends on the ratio of modulator to histone and the resultant state of the complex formed (better or poorer substrate than free histone). The observed effect is also dependent on the properties of the histone substrate as Michaelis-Menten kinetics are not observed in the phosphorylation of arginine-rich histone in the absence or presence of cyclic GMP.

Animals↗
PubMed1988

Time domain reflectrometry: the difference method applied to conductive aqueous solutions.

The precision difference time domain reflectrometry method has been developed for application to conductive aqueous solutions. The sensitivity of the technique has been investigated with protein and polypeptide solutions over the frequency range 100 kHz to 1 GHz. Loss processes with an absorption maximum of 0.3 have been successfully measured and larger dispersions characterised in KCl concentrations as high as 100 mM.

Electric Conductivity↗
PubMed1991

Vitamin K-dependent carboxylation of poly-L-glutamate.

Poly-L-glutamate preparations of varying chain length were used as substrates for bovine liver vitamin K-dependent carboxylase. The quality of these substrates (as measured by their apparent kinetic constants) was comparable to that of the more commonly used tri- and pentapeptides, but the maximal reaction rate increased at increasing chain length.

Animals↗
PubMed1995

Immunocytochemical comparison of posttranslationally modified forms of tubulin in the vestibular end-organs of the gerbil: tyrosinated, acetylated and polyglutamylated tubulin.

Specific antibodies against alpha-tubulin, acetylated alpha-tubulin, tyrosinated alpha-tubulin and polyglutamylated alpha- and beta-tubulin were used to compare the distribution of posttranslationally modified tubulin in the vestibular end-organs of the gerbil. Antibodies to acetylated tubulin labeled a dense network of microtubules in the hair cells and bundles of microtubule in the supporting cells. Nerve fibers within and below the epithelium were weakly labeled. This localization paralleled that seen with antibodies to alpha-tubulin which labeled all microtubules present in the cells. Antibodies to tyrosinated tubulin labeled networks and bundles of microtubules in both hair cells and supporting cells and in addition gave intense, diffuse labeling in the cytoplasm of both cell types. It also labeled the nerve fibers. Antibodies to polyglutamylated tubulin were localized mainly in nerve fibers, and in the calyces the labeled microtubules were found running circumferentially around the type I sensory hair cells. Thus, tyrosinated tubulin was found in the fine networks of microtubules in both the sensory and supporting cells. Acetylated tubulin was found in the dense networks and bundles of microtubules in the sensory and supporting cells, but did not colocalize with polyglutamylated tubulin, which was found predominantly in the nerve fibers. The labeling patterns for the tyrosinated tubulin and posttranslationally modified tubulins in the sensory and supporting cells of the vestibular end organs differ from that seen in the organ of Corti and may reflect differences in the stability of the microtubules and the mechanical properties of the sensory epithelium.

Acetylation↗