Structure-based design and characterization of a Novel IL-6 antagonist peptide.
The development of rational methods to design antagonist peptides based on the 3-D structure of protein active region has, to now, been only marginally successful. This has been largely due to the difficulty of constraining the recognition elements of a mimetic structure to the relative conformational and spatial orientations present in the parent molecule. According to the 3-D complex structure of human interleukin-6 (hIL-6) and its receptor (hIL-6R), a novel antagonist peptide (named PT), which possessed potential bioactivity of hIL-6, was designed by the means of distance geometry, molecular modeling and molecular dynamics trajectory analysis. The bioactivity of the designed peptide (i.e. PT) was evaluated using XG-7 cells, a hIL-6-dependent B-cell line. PT possessed potential bioactivity to antagonize the function of hIL-6 and could efficiently induce the growth arrest and apoptosis of XG-7 cells in a dose-dependent manner.
Yang
Zhenhui
Z
Institute of Basic Medical Sciences, P.O. Box 130 (3), Taiping Road, Beijing 100850, PR China.
Feng
Jiannan
J
Li
Yan
Y
Hu
Meiru
M
Song
Lun
L
Yu
Ming
M
Qin
Weisong
W
Shen
Beifen
B
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D010455:Peptides; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors