N-Sulfonyl-β-lactam hapten as an effective labeling reagent for aldolase mAb

Bioorg Med Chem Lett. 2015 Apr 15;25(8):1684-1687. doi: 10.1016/j.bmcl.2015.03.011. Epub 2015 Mar 10.

Abstract

Utilization of chemically programmed antibodies (cpAbs) is regarded to be one of the most efficient methods for the development of therapeutic systems. cpAbs can extend the half-life of programming reagents, activate immune systems via the Fc region of antibodies and achieve universal vaccination by attaching varieties of small, programmed molecules. In the current study, we aimed to develop a novel labeling reagent for the preparation of cpAbs and found that N-sulfonyl-β-lactams (NSBLs) were optimal. NSBL can be synthesized from readily available 4-(bromomethyl)benzenesulfonyl chloride via few simple manipulations and can label the aldolase monoclonal antibody (mAb) 84G3, which could not be labeled effectively by the conventional labeling reagent, N-acyl-β-lactam (NABL). We also demonstrated that the conjugate, which consists of mAb 84G3 and an NSBL bearing a biotin moiety, maintained strong binding activity to streptavidin. In addition, the stability assay of NSBL revealed that NSBLs can tolerate aqueous media without significant decomposition over 24h.

Keywords: Aldolase antibody; Bioconjugation; Chemically programmed antibody; N-Sulfonyl-β-lactam.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antigen-Antibody Reactions
  • Biotin / chemistry
  • Biotin / metabolism
  • Fructose-Bisphosphate Aldolase / chemistry*
  • Fructose-Bisphosphate Aldolase / immunology
  • Haptens / chemistry*
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / immunology
  • Protein Binding
  • Protein Stability
  • Streptavidin / chemistry
  • Streptavidin / metabolism
  • beta-Lactams / chemistry*

Substances

  • Antibodies, Monoclonal
  • Haptens
  • Immunoglobulin Fab Fragments
  • beta-Lactams
  • Biotin
  • Streptavidin
  • antibody aldolase
  • Fructose-Bisphosphate Aldolase