Stabilized Cyclic Peptides as Scavengers of Autoantibodies: Neutralization of Anticitrullinated Protein/Peptide Antibodies in Rheumatoid Arthritis

ACS Chem Biol. 2018 Jun 15;13(6):1525-1535. doi: 10.1021/acschembio.8b00118. Epub 2018 May 24.


The occurrence of autoantibodies is a hallmark of rheumatoid arthritis, specifically those autoantibodies targeting proteins containing the arginine-derived amino acid citrulline. There is strong evidence showing that the occurrence of anticitrullinated protein/peptide antibodies (ACPA) are involved in disease progression, and ACPA was recently shown to induce pain in animals. Here, we explore a novel concept useful for research, diagnostics, and possibly therapy of autoimmune diseases, namely, to directly target and neutralize autoantibodies using peptide binders. A high-affinity peptide-based scavenger of ACPA was developed by grafting a citrullinated epitope derived from human fibrinogen into a naturally occurring stable peptide scaffold. The best scavenger comprises the truncated epitope α-fibrinogen, [Cit573]fib(566-580), grafted into the scaffold sunflower trypsin inhibitor-1, SFTI-1. The final peptide demonstrates low nanomolar apparent affinity and superior stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Citrullinated Protein Antibodies / immunology*
  • Arthritis, Rheumatoid / diagnosis*
  • Cyclization
  • Drug Design
  • Epitopes
  • Fibrinogen / chemical synthesis
  • Fibrinogen / chemistry
  • Fibrinogen / immunology
  • Helianthus / chemistry
  • Humans
  • Molecular Structure
  • Momordica / chemistry
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / immunology*
  • Protein Binding
  • Protein Stability


  • Anti-Citrullinated Protein Antibodies
  • Epitopes
  • Peptide Fragments
  • Peptides, Cyclic
  • SFTI-1 peptide, sunflower
  • Fibrinogen