Structure-based design and characterization of a Novel IL-6 antagonist peptide

• DOI: 10.1016/j.molimm.2004.09.033
• Publication Date: 2004-12-15T16:26:12Z
• Authors: Zhenhui Yang; Jiannan Feng; Yan Li; Meiru Hu; Lun Song; Ming Yu; Weisong Qin; Beifen Shen
• Keywords: Rational design

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.