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An Immunomodulatory Peptide Dendrimer Inspired from Glatiramer Acetate

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Erzina Dina, Capecchi Alice, Javor Sacha, Reymond Jean‐Louis,
Project Chemical Space Design of Small Molecules and Peptides
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Original article (peer-reviewed)

Journal Angewandte Chemie International Edition
Volume (Issue) 60(50)
Page(s) 26403 - 26408
Title of proceedings Angewandte Chemie International Edition
DOI 10.1002/anie.v60.50

Open Access

URL http://doi.org/10.1002/anie.v60.50
Type of Open Access Publisher (Gold Open Access)

Abstract

Glatiramer acetate (GA) is a random polypeptide drug used to treat multiple sclerosis (MS), a chronic autoimmune disease. With the aim of identifying a precisely defined alternative to GA, we synthesized a library of peptide dendrimers with an amino acid composition similar to GA. We then challenged the dendrimers to trigger the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) from human monocytes, which is one of the effects of GA on immune cells. Several of the largest dendrimers tested were as active as GA. Detailed profiling of the best hit showed that this dendrimer induces the differentiation of monocytes towards an M2 (anti-inflammatory) state as GA does, however with a distinct immune marker profile. Our peptide dendrimer might serve as starting point to develop a well-defined immunomodulatory analog of GA.
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