Interleukin 10 (IL-10) is a cytokine that is able to downregulate inflammation. Its overexpression is directly associated with the difficulty in the clearance of chronic viral infections, such as chronic hepatitis B, hepatitis C and HIV infection, and infection-related cancer. IL-10 signaling blockade has been proposed as a promising way of clearing chronic viral infection and preventing tumor growth in animal models. Recently, we have reported that peptides with a helical repeating pattern of hydrophobic and hydrophilic residues are able to inhibit IL-10 significantly both in vitro and in vivo1 Ni G, Chen S, Yang Y, Cummins SF, Zhan J, Li Z, et al. Investigation the Possibility of Using Peptides with a Helical Repeating Pattern of Hydro-Phobic and Hydrophilic Residues to Inhibit IL-10. PLoS One 2016; 11:e0153939. . In this work, we seek to further study the inhibiting mechanism of these peptides using sequence-modified peptides. As evidenced by both experimental and molecular dynamics simulation in concert the N-terminal hydrophobic peptide constructed with repeating hydrophobic and hydrophilic pattern of residues is more likely to inhibit IL10. In addition, the sequence length and the ability of protonation are also important for inhibition activity.
Human Vaccines & Immunotherapeutics / Vol. 13, No. 3, pp.518-527