Synthesis of selected LeY and KH-1 analogues: a medicinal chemistry approach to vaccine optimization

J Org Chem. 2005 Apr 29;70(9):3383-95. doi: 10.1021/jo048016l.

Abstract

[structure: see text] As part of our ongoing anticancer vaccine program, we recently found that antibodies generated in response to the KH-1-KLH construct recognized not only KH-1 antigen but also the Lewis Y (Le(y)) antigen as well, with antibody titer levels much higher than those observed after immunization with individual Le(y)-KLH vaccine constructs. In an attempt to explore the structure-antigenic relationship of these carbohydrate epitopes, several analogues of both KH-1 and Le(y) were synthesized. A convergent synthetic approach to the analogues was designed on the basis of well-established glycal methodology, employing a minimum number of building blocks to generate competent antigens with high stereoselectivity and reasonable yield.

MeSH terms

  • Adjuvants, Immunologic
  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Cancer Vaccines / chemical synthesis*
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Carbohydrate Sequence
  • Chemistry, Pharmaceutical / methods
  • Immunization
  • Lewis Blood Group Antigens / immunology*
  • Molecular Structure
  • Oligosaccharides / chemistry
  • Oligosaccharides / immunology
  • Structure-Activity Relationship
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Tumor-Associated, Carbohydrate
  • Cancer Vaccines
  • Lewis Blood Group Antigens
  • Lewis Y antigen
  • Oligosaccharides
  • Vaccines, Synthetic
  • antigen KH-1