Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Dm, Moran; Aw, Wheeler; Dc, Henderson; Whittall, Neil

doi:10.1159/000234163

Cited by 6 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intravenous treatment of mice with conjugates of polysarcosine-allergen have previously been shown to suppress the induction of an IgE response and to impair a secondary response in sub-lethally irradiated recipients [11,19]. Activity was demonstrated to be specific and was maintained in the absence of further challenge.…”

Section: Discussionmentioning

confidence: 99%

“…We have described previously the suppressive ef fects of conjugates of poly-N-methyl glycine (polysarcosine)-grass pollen extracts on the induction and maintenance of IgE responses in mice [11,19,20]. The present report is concerned with the effects of these conjugates on lymphocyte activity in culture, and possible mechanisms of action are discussed.…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Cook¹,

Henderson²,

Wheeler³

et al. 1986

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen allergen extracts, which have been previously shown to suppress murine IgE responses, were examined for their ability to modify lymphocyte activity in vitro. Allergen-specific T lymphocytes obtained from Balb/c mice gave a reduced response to syngeneic accessory cells pulsed with conjugates of polysarcosine-allergen compared with the response found using equivalent concentrations of native extract. Pretreatment of accessory cells with either polysarcosine or polysarcosine-allergen conjugates did not impair their subsequent ability to present grass pollen extract to immune T cells. Incubation of allergen-specific spleen cells with polysarcosine-allergen conjugates, but not with polysarcosine or allergen alone, resulted in specific cell-mediated suppression which significantly reduced proliferation in vitro. This activity was sensitive to treatment of cells with anti-T-lymphocyte antisera plus complement. Spleen cells obtained from animals immunised with allergen and taken 21 days after intravenous treatment with polysarcosine-allergen conjugates, a regimen that suppressed IgE antibody production, did not proliferate in the presence of grass pollen extract and failed to suppress a secondary lymphoproliferative response in vitro. Spleen cells obtained from similarly treated animals 3 days after the final polysarcosine-allergen injection responded to pollen extract in culture and, additionally, impaired a secondary response. The results suggest that the reduced IgE response found in animals treated with polysarcosine-allergen conjugates may be due, in part, to the generation of a short-lived antigen-specific T cell suppression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Cook¹,

Henderson²,

Wheeler³

et al. 1986

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

“…The suppression is allergen-specific and requires covalent linking of the polysarcosine to the allergen. [92] The reduced IgE response was transient [93] and was attributed partly to a short-lived antigen-specific T cell suppression. [94] It was further demonstrated that intranasal application of the conjugate can reduce the serum IgE antibody response that was brought about through exposure to the grass pollen extract, [95] providing a method to treat allergy.…”

Section: Immunogenicitymentioning

confidence: 99%

Polypeptoid polymers: Synthesis, characterization, and properties

et al. 2017

View full text Add to dashboard Cite

Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids. | I N TR ODU C TI ONPolypeptoids composed of N-substituted polyglycine backbones are structural mimics of polypeptides ( Figure 1). Because of N-substitution, polypeptoids lack stereogenic centers and hydrogen bonding interactions along the main chains, in sharp contrast to polypeptides.As a result, the global conformations of polypeptoids are strongly dependent on the N-substituent structures, giving rise to random coils or well-defined secondary structures [eg, polyproline I (PPI) helix [1][2][3][4][5][6] and R-sheets] [7][8][9][10][11][12] that are reminiscent of those of polypeptides. The polypeptoid backbone containing tertiary amide linkages is highly polar and hydrophilic. The physicochemical properties of polypeptoids can be tailored by the N-substituent structures, enabling control over the hydrophilicity and lipophilicity balance (HLB), charge characteristics, [13,14] backbone conformation, [1][2][3][4][5][6][7][8][9][10][11][12] solubility, [15][16][17][18][19][20] thermal and crystallization properties of the polypeptoids. [21][22][23][24] Without extensive hydrogen bonding, polypeptoids are thermally processable similar to conventional thermoplastics, [20][21][22][23][24] whereas polypeptides undergo thermal degradation before they can be melt-processed due to the extensive hydrogen bonding interactions. While polypeptoids exhibited enhanced proteolytic stability relative to peptides, [25,26] they can be oxidatively degraded under conditions that mimic tissue inflammation, [27] suggesting their potential in vivo uses as biodegradable materials.Recent advances in the controlled polymerization methods have enabled access to a suite of structurally well-defined polypeptoids with various N-substituent structures and molecular architectures, setting the stage for the future development of polypeptoid materials for various targeted applications. Several review articles on the synthesis, properties, and application of polypeptoids for biomedical or nonbiomedical uses have been published in recent years. [28][29][30][31][32] As a result, this...

show abstract

“…Such conjugates have been shown to have the capacity to sup press IgE antibody responses in mice [13,19].…”

Section: Conjugate Of Polysarcosine and Mixed Grass Pollen Extractmentioning

confidence: 99%

“…In addition, we have shown that tolerogenic forms of pollen allergen, conjugates of grass pollen extracts and polysarcosine, poly-(N-methylglycine), given parenterally to mice, were capable of suppressing spe cific IgE antibody production [13,19,20], These find ings indicated that continuous therapy with such tolerogens during the period of environmental exposure to allergen could prevent the seasonal boost of IgE antibody production and concomitant heightened sensitivity in susceptible individuals. The problems associated with systemic therapy may be avoided by use of the intranasal route and, therefore, we have ex plored the possibility of suppressing IgE responses in mice by intranasal administration of these tolerogenic preparations.…”

Section: Introductionmentioning

confidence: 99%

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Dc¹,

Aw²,

Dm³

1987

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

Serum IgE antibody responses were generated in mice by intranasal exposure to grass pollen extract. Primary IgE responses were suppressed by the concomitant intranasal administration of a conjugate of polysarcosine and pollen extract which has been shown to be a potent tolerogen when given parenterally. Partial suppression of boosted IgE responses was observed when the conjugate was applied intranasally with a secondary challenge of unmodified extract. The data suggest that clinical schedules of intranasal application of tolerogenic conjugates can be devised to bring about specific IgE suppression.

show abstract

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Cited by 6 publications

References 5 publications

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Polypeptoid polymers: Synthesis, characterization, and properties

Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Contact Info

Product

Resources

About