Multivalent thioether-peptide conjugates: B cell tolerance of an anti-peptide immune response

Bioconjug Chem. 1999 May-Jun;10(3):480-8. doi: 10.1021/bc9801373.

Abstract

Antibodies which bind beta2-glycoprotein I (beta2GPI) are associated with antiphospholipid syndrome. Synthetic peptide mimotopes have been discovered which compete with beta2GPI for binding to selected anti-beta2GPI. A thiol-containing linker was attached to the N-terminus of two cyclic thioether peptide mimotopes, peptides 1a and 1b. The resulting peptides, with linker attached, were reacted with two different haloacetylated platforms to prepare four tetravalent peptide-platform conjugates to be tested as B cell toleragens. The linker-containing peptides were reacted with maleimide-derivatized keyhole limpet hemocyanin (KLH) to provide peptide-KLH conjugates. Peptides 1a and 1b were also modified by acylation with 3-(4'-hydroxyphenyl)propionic acid N-hydroxysuccinimidyl ester. The resulting hydroxyphenyl peptides were radioiodinated and used to measure anti-peptide antibody levels. The KLH conjugates were used to immunize mice to generate an anti-peptide immune response. The immunized mice were treated with the conjugates or saline solution and boosted with the appropriate peptide-KLH conjugate. Three of the four conjugates suppressed the formation of anti-peptide antibody. The stabilities of the conjugates in mouse serum were measured, and the relative stabilities did not correlate with ability to suppress antibody formation.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Hemocyanins / chemistry
  • Hemocyanins / immunology
  • Immune Tolerance*
  • Immunity
  • Mice
  • Peptides / chemistry*
  • Peptides / immunology
  • Sulfhydryl Compounds / chemistry
  • Sulfides / chemistry*
  • Sulfides / immunology

Substances

  • Peptides
  • Sulfhydryl Compounds
  • Sulfides
  • Hemocyanins
  • keyhole-limpet hemocyanin