Chun‑Chun Changa,†, Cheng‑Der Liub,†, Sheng‑Feng Panc, Wei‑Han Huangd, Chih‑Wen Pengb*, Hao‑Jen Hsuc,e*
aDepartment of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, bInstitute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, cDepartment of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan, dDepartment of Oncology and Hematology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, eDepartment of Life Sciences, Tzu Chi University, Hualien, Taiwan
†These authors contributed equally to this work.
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Objective: Human interleukin‑10 (IL‑10) is a dimeric and pleiotropic cytokine that plays a crucial role in cellular immunoregulatory responses. As IL‑10 binds to its receptors, IL‑10Ra and IL‑10Rb, it will suppress or induce the downstream cellular immune responses to protect from diseases. Materials and Methods: In this study, a potential peptide derived from IL‑10 based on molecular docking and structural analysis was designed and validated by a series of cell assays to block IL‑10 binding to receptor IL‑10Ra for the inhibition of cell growth. Results: The simulation results indicate that the designed peptide IL10NM25 bound to receptor IL‑10Ra is dominated by electrostatic interactions, whereas van der Waals (VDW) and hydrophobic interactions are minor. The cell experiments showed that IL10NM25 specifically binds to receptor IL‑10Ra on the cell surface of two B‑lineage cell lines, B lymphoma derived (BJAB), and lymphoblastoid cell line, whereas the mutant and scramble peptides are not able to suppress the binding of IL‑10 to receptor IL‑10Ra consistent with the molecular simulation predictions. Conclusion: This study demonstrates that structure‑based peptide design can be effective in the development of peptide drug discovery.
Keywords: Cytokine, Interleukin‑10, Molecular docking, Peptide design
