Identification and synthesis of an efficient multivalent E. coli heat labile toxin inhibitor __ A dynamic combinatorial chemistry approach

Bioorg Med Chem. 2020 May 1;28(9):115436. doi: 10.1016/j.bmc.2020.115436. Epub 2020 Mar 13.

Abstract

A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.

Keywords: Dynamic combinatorial chemistry; E. coli heat labile toxin; Multivalent interaction; Protein inhibition; Supramolecular chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / pharmacology*
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Combinatorial Chemistry Techniques*
  • Dose-Response Relationship, Drug
  • Enterotoxins / antagonists & inhibitors*
  • Enterotoxins / metabolism
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / metabolism
  • Galactose / chemistry
  • Galactose / pharmacology*
  • Humans
  • Hydrazines / chemistry
  • Hydrazines / pharmacology*
  • Molecular Structure
  • Propylene Glycols / chemistry
  • Propylene Glycols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Hydrazines
  • Propylene Glycols
  • polyglycidol
  • heat-labile enterotoxin, E coli
  • Galactose