New muramyl dipeptide (MDP) mimics without the carbohydrate moiety as potential adjuvant candidates for a therapeutic hepatitis B vaccine (HBV)

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4292-5. doi: 10.1016/j.bmcl.2011.05.056. Epub 2011 May 25.

Abstract

A series of new muramyl dipeptide (MDP) mimics were designed and synthesized via a solid-phase synthetic route. Their adjuvant activities were evaluated ex vivo for investigation of the synergism of the S(28-39) peptide, which is an MHC class I binding epitope of recombinant hepatitis B surface antigen (HBsAg) for both humans and mice. Several compounds without the carbohydrate moiety exerted better adjuvanticity than the MDP-C that has been reported by our laboratory previously. A primary screening test revealed that compounds 6, 14 and 16 exhibited stronger adjuvanticity compared with other MDP mimics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / chemical synthesis
  • Acetylmuramyl-Alanyl-Isoglutamine / chemistry*
  • Acetylmuramyl-Alanyl-Isoglutamine / immunology
  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • Carbohydrates / chemistry
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Adjuvants, Immunologic
  • Carbohydrates
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Recombinant Proteins
  • Acetylmuramyl-Alanyl-Isoglutamine