Identification and synthesis of a receptor binding site of human anaphylatoxin C5a

J Med Chem. 1991 Jul;34(7):2068-71. doi: 10.1021/jm00111a022.

Abstract

C5a is a 74 amino acid polypeptide that likely plays an important role in the pathogenesis of a number of inflammatory diseases. Therefore, the discovery of a C5a antagonist is of considerable therapeutic interest. A series of peptides designed to survey various regions of the molecule was synthesized by solid-phase peptide synthesis and evaluated for receptor-binding activity with polymorphonuclear leukocyte membranes. The C-terminal octapeptide (Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) was identified as the smallest fragment which possessed reasonable C5a receptor binding activity.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Binding, Competitive / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Complement C5a / antagonists & inhibitors
  • Complement C5a / metabolism*
  • Humans
  • Molecular Sequence Data
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / pharmacology
  • Receptors, Complement / drug effects
  • Receptors, Complement / metabolism*

Substances

  • Oligopeptides
  • Peptide Fragments
  • Receptors, Complement
  • acetylhistidyl-lysyl-aspartyl-methionyl-glutaminyl-leucyl-glycyl-arginine
  • Complement C5a