TY - JOUR
T1 - Characterization of linear mimetic peptides of Interleukin-22 from dissection of protein interfaces
AU - La Manna, Sara
AU - Scognamiglio, Pasqualina Liana
AU - Di Natale, Concetta
AU - Leone, Marilisa
AU - Mercurio, Flavia Anna
AU - Malfitano, Anna Maria
AU - Cianfarani, Francesca
AU - Madonna, Stefania
AU - Caravella, Sergio
AU - Albanesi, Cristina
AU - Novellino, Ettore
AU - Marasco, Daniela
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Interleukin-22 (IL-22) belongs to the family of IL-10 cytokines and is involved in a wide number of human diseases, including inflammatory disorders and cancer pathology. The ligand-receptor complex IL-22/IL-22R plays a key role in several pathways especially in the regulation and resolution of immune responses. The identification of novel compounds able to modulate IL-22/IL-22R complex could open the route to new therapeutic strategies in multiple human diseases. In this study, we designed and characterized IL-22 derived peptides at protein interface regions: several sequences revealed able to interfere with the protein complex with IC50 in the micromolar range as evaluated through Surface Plasmon Resonance (SPR) experiments. Their conformational characterization was carried out through Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopies, shedding new light into the features of IL-22 fragments and on structural determinants of IL-22/IL-22R1 recognition. Finally, several peptides were tested on human keratinocyte cultures for evaluating their ability to mimic the activation of molecular pathways downstream to IL-22R in response to IL-22 binding.
AB - Interleukin-22 (IL-22) belongs to the family of IL-10 cytokines and is involved in a wide number of human diseases, including inflammatory disorders and cancer pathology. The ligand-receptor complex IL-22/IL-22R plays a key role in several pathways especially in the regulation and resolution of immune responses. The identification of novel compounds able to modulate IL-22/IL-22R complex could open the route to new therapeutic strategies in multiple human diseases. In this study, we designed and characterized IL-22 derived peptides at protein interface regions: several sequences revealed able to interfere with the protein complex with IC50 in the micromolar range as evaluated through Surface Plasmon Resonance (SPR) experiments. Their conformational characterization was carried out through Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR) spectroscopies, shedding new light into the features of IL-22 fragments and on structural determinants of IL-22/IL-22R1 recognition. Finally, several peptides were tested on human keratinocyte cultures for evaluating their ability to mimic the activation of molecular pathways downstream to IL-22R in response to IL-22 binding.
KW - Circular dichroism
KW - IL-22 signalling
KW - Interface protein regions
UR - http://www.scopus.com/inward/record.url?scp=85018363234&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018363234&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2017.05.002
DO - 10.1016/j.biochi.2017.05.002
M3 - Article
C2 - 28479106
AN - SCOPUS:85018363234
SN - 0300-9084
VL - 138
SP - 106
EP - 115
JO - Biochimie
JF - Biochimie
ER -