دورية
Rational design of granulocyte-macrophage colony-stimulating factor antagonist peptides.
| العنوان: | Rational design of granulocyte-macrophage colony-stimulating factor antagonist peptides. |
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| المؤلفون: | Monfardini, C, Kieber-Emmons, T, Voet, D, Godillot, A P, Weiner, D B, Williams, W V |
| المصدر: | Journal of Biological Chemistry; February 1996, Vol. 271 Issue: 6 p2966-71, 6p |
| مستخلص: | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the four-helix bundle family of cytokines/growth factors which exhibit several activities. It is a hematopoietic growth factor, a cytokine involved in inflammatory and immune processes, an adjunct for cancer therapy, and an anti-tumor immunomodulator. Studies of interactions between GM-CSF and its receptor and identification of small peptides presenting binding capacity to the receptor are important goals for the development of GM-CSF analogs. Here we describe the study of two cyclic peptides, 1785 and 1786, developed based on structural analysis of the GM-CSF region mimicked by anti-anti-GM-CSF recombinant antibody 23.2. These peptides were designed to structurally mimic the positions of specific residues on the B and C helices of human GM-CSF implicated in receptor binding and bioactivity. Both 1785 and 1786 were specifically recognized by polyclonal anti-GM-CSF antibody (stronger for 1786 than 1785). 1786 also competitively inhibited binding of GM-CSF to the GM-CSF receptor on HL-60 cells and demonstrated antagonist bioactivity, as shown by its reversal of GM-CSF's ability to inhibit apoptosis of the GM-CSF-dependent cell line MO7E. These studies support the role of residues on the GM-CSF B and C helices in receptor binding and bioactivity and suggest strategies for mimicking binding sites on four-helix bundle proteins with cyclic peptides. |
| قاعدة البيانات: | Supplemental Index |
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