title: A novel hIL-6 antagonist peptide from computer-aided design contributes to suppression of apoptosis in M1 cells.
abstract: Based on the complex crystal structure of human interleukin-6 (hIL-6) and its receptor (hIL-6R), a novel hIL-6 antagonist peptide (named PT) was designed using computer-guided design method. Dealing with molecular docking and molecular dynamics methods, the interaction between PT and hIL-6R was analyzed. The theoretical studies showed that PT possessed very high affinity to hIL-6R and offered a practical means of imposing long-term blockade of hIL-6 activity in vivo. This effect was examined due to growth arrest and apoptosis induced by hIL-6 in myeloblastic cell line M1 cells in a dose-dependent manner. The findings demonstrate that PT could also act as an excellent antagonist candidate for the induction of growth arrest and apoptosis. Furthermore, murine M1 myeloid cell line, which was induced by the physiological inducer hIL-6 to undergo apoptosis and growth arrest, could be used as a subtle model system to test hIL-6 antagonist.
authors.affiliation: Institute of Basic Medical Sciences, P.O. Box 130 (3), Taiping Road, Beijing 100850, PR China.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Yang
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Meiru
authors.initials: M
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Weisong
authors.initials: W
authors.lastname: Qin
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D010455:Peptides; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors