26 research outputs found
A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11
Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11RΞ± is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11RΞ± has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs
Advancement and applications of peptide phage display technology in biomedical science
Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery
Use of a modified bacteriophage to probe the interactions between peptides and ion channel receptors in mammalian cells
Peptide immobilized on gold particles enhances cell growth
A multivalent ligand of thrombopoietin (TPO) was prepared by immobilization of mimetic peptides on gold particles. An effective peptide ligand containing cysteine was designed to enhance the growth of TPO-sensitive cells. The peptide was then immobilized on gold particles by self assembly. The multivalent ligand enhanced the growth of TPO-dependent cells and its activity was more than that of the monovalent ligand