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

Gunasekera S, Fernandes-Cerqueira C, Wennmalm S, Wähämaa H, Sommarin Y, Catrina AI, Jakobsson PJ, Göransson U

ACS Chem. Biol. 13 (6) 1525-1535 [2018-06-15; online 2018-04-09]

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 alpha-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.

Advanced Light Microscopy (ALM) [Collaborative]

Swedish NMR Centre (SNC) [Service]

QC bibliography QC xrefs

DOI 10.1021/acschembio.8b00118

Crossref 10.1021/acschembio.8b00118

Stefan Wennmalm collaboration (FCS)