Stabilized cyclic peptides as scavengers of autoantibodies: neutralization of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis

Sunithi Gunasekera, Catia Fernandes-Cerqueira, Stefan Wennmalm, Heidi Wähämaa, Yngve Sommarin, Anca I. Catrina, Per-Johan Jakobsson, Ulf Göransson

Index: 10.1021/acschembio.8b00118

Full Text: HTML

Abstract

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 anti-citrullinated 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.