ISSN:
1573-6776
Keywords:
affinity panning
;
antagonist
;
interleukin-6
;
peptide ligand
;
Stat3
Source:
Springer Online Journal Archives 1860-2000
Topics:
Process Engineering, Biotechnology, Nutrition Technology
Notes:
Abstract To develop a small peptide antagonist for a cytokine, an oligopeptide ligand interacting with interleukin-6 (IL-6) has been screened by affinity panning from a random heptapeptide displaying phage library. After biopanning five times against IL-6, ten phages displaying heptapeptides with consensus sequence, K(L/V)WXIPQ, were selected out of nucleotide sequencing of 21 phages. A synthetic oligopeptide, KLWTIPQ (P-1), was prepared but it did not inhibit growth of MH60, an IL-6 dependent cell line. To stabilize the structure of oligopeptide and bring stronger molecular hindrance In interaction between IL-6 and its two receptors (IL-6R and gp130), a peptide with two cysteine residues at each end of consensus sequence, GGCKLWTIPQCGG (PC), was also synthesized, which significantly inhibited cell growth of MH60 at over 100 μM and phosphorylation of Stat3, which is primary signal transducer and activator of transcription, phosphorylated by IL-6 signal. These results strongly suggest that PC is specifically bound to IL-6 and hinders formation of IL-6/IL-6R/gp130 complex.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005605808186
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