Allylmalonamide as a bivalent linker: synthesis of biantennary GM3-saccharide--keyhole limpet hemocyanin glycoconjugate and the immune response in mice

Glycoconj J. 1999 Sep;16(9):507-15. doi: 10.1023/a:1007069904462.

Abstract

A biantennary GM3-saccharide (sialyllactoside) derivative (4) was constructed using allylmalonic acid as a bivalent linker, both carboxylic acids of which were condensed with 3-aminopropyl lactoside (2) prior to enzymatic sialylation with a fusion enzyme. While ozonolysis of its allyl group generated a saccharide having a terminal aldehyde (6), we were unable to couple 6 directly to protein by reductive amination. However, extension of the spacer by means of introducing a maleimide group to 6 through its aldehyde group to give 7 enabled the latter to be successfully coupled to thiolated proteins. The average ratios of saccharide to protein were observed to be 35 in KLH conjugate (13) and 9-12 in HSA conjugates (14 and 15). The antisera obtained by immunizing mice with the biantennary sialyllactoside-KLH conjugate (13) together with MPL adjuvant were analyzed by ELISA. Using several structurally related saccharide-HSA conjugates as screening antigens, it was concluded that anti-sialyllactoside antibodies, both IgG and IgM, were effectively raised. This was further supported by competitive inhibition experiments using lactoside (1), sialyllactoside (8) and biantennary sialyllactoside (4) as inhibitors.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Allyl Compounds / chemistry*
  • Animals
  • Antibody Formation
  • Carbohydrate Sequence
  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents / chemistry*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • G(M3) Ganglioside / chemistry*
  • Glycoconjugates / chemical synthesis*
  • Glycoconjugates / immunology
  • Hemocyanins / chemistry*
  • Magnetic Resonance Spectroscopy
  • Malonates / chemistry*
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data

Substances

  • Adjuvants, Immunologic
  • Allyl Compounds
  • Cross-Linking Reagents
  • G(M3) Ganglioside
  • Glycoconjugates
  • Malonates
  • allylmalonic acid
  • Hemocyanins
  • keyhole-limpet hemocyanin