Inhibitory mechanism of peptides with a repeating hydrophobic and hydrophilic residue pattern on interleukin-10.
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 vivo.1In 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.
a Genecology Research Centre , University of the Sunshine Coast , Maroochydore , DC , Australia.|b School of Medical Science, Griffith Health Institute , Griffith University , Gold Coast , Australia.
Guoying
G
Ni
c Cancer Research Institute, Foshan First People's Hospital , Foshan , Guangdong , China.
Yuejian
Y
Wang
a Genecology Research Centre , University of the Sunshine Coast , Maroochydore , DC , Australia.
Scott
S
Cummins
d Inflammation and Healing Research Cluster, School of Health and Sport Sciences , University of Sunshine Coast , Maroochydore , DC , Australia.
Shelley
S
Walton
d Inflammation and Healing Research Cluster, School of Health and Sport Sciences , University of Sunshine Coast , Maroochydore , DC , Australia.
Kate
K
Mounsey
c Cancer Research Institute, Foshan First People's Hospital , Foshan , Guangdong , China.|d Inflammation and Healing Research Cluster, School of Health and Sport Sciences , University of Sunshine Coast , Maroochydore , DC , Australia.
Xiaosong
X
Liu
b School of Medical Science, Griffith Health Institute , Griffith University , Gold Coast , Australia.
Ming Q
MQ
Wei
a Genecology Research Centre , University of the Sunshine Coast , Maroochydore , DC , Australia.
Tianfang
T
Wang
D002460:Cell Line; D002942:Circular Dichroism; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D020349:Surface Plasmon Resonance
D007155:Immunologic Factors; D010455:Peptides; D016753:Interleukin-10
ELISA; circular dichroism spectroscopy; interleukin-10 inhibiting peptide; interleukin-10 receptor; molecular dynamic simulation; surface plasmon resonance spectroscopy
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