Pachymodulin, a new functional formyl peptide receptor 2 (FPR2) peptidic ligand isolated from frog skin, has Janus-like immunomodulatory capacities

Claire Lacombe, Christophe Piesse, Sandrine Sagan, Christophe Combadiere, Yvonne Rosenstein, and Constance Auvynet, J. Med. Chem., 2015, 58, 1089-1099.

Recruitment of leukocytes is essential in order to fight infections or to heal injuries; however excessive and/or prolonged responses favor the development of major inflammatory pathologies, such as cardiovascular or neurodegenerative diseases. Thus, it is of great interest to seek for novel compounds that can regulate leukocytes recruitment depending on the degree of inflammation. We have isolated and characterized by different chromatographic techniques, mass spectrometry and Edman sequencing a new hexapeptide (SSLSKL) from the Mexican frog Pachymedusa dacnicolor, which we named Pachymodulin. In vitro, pachymodulin promotes the migration of leukocytes through the binding and activation of the human and mouse N-formyl peptide receptor 2 (huFPR2). In vivo, it exhibits opposite biological activities: under homeostatic conditions, pachymodulin induces the recruitment of leukocytes, whereas under inflammatory conditions, it inhibits this process. Therefore, Pachymodulin represents an interesting template in the quest to design new immunomodulatory drugs in the therapy of immune-related diseases.

Copyright © 2015 American Chemical Society