In Vitro Selection of a Peptide Inhibitor of Human IL-6 Using mRNA Display |
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Authors: | Teruaki Kobayashi Minako Kakui Tatsuro Shibui Yasunori Kitano |
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Institution: | (1) ZoeGene Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-8502, Japan;(2) Present address: MOLECUENCE Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-8502, Japan |
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Abstract: | Interleukin-6 (IL-6) plays a crucial role in malignant diseases, such as rheumatoid arthritis, Castleman disease, and multiple
myeloma, and as such, is an attractive therapeutic target. Here, the authors isolated a novel IL-6 inhibitor peptide by in
vitro selection using mRNA display. The authors first used a random-primed human cDNA library to isolate IL-6-binding peptides.
After four rounds of selection, a 19-amino acid peptide named CA11 was selected and confirmed to specifically interact with
IL-6. The authors then performed an alanine scan analysis of CA11 and determined the amino acid residues necessary to interact
with IL-6. Next, the authors constructed a CA11-based partially randomized library and after ten more rounds of selection,
isolated several groups of peptides. The most frequently occurring sequence, RA07, bound to IL-6 with 3 to 4-fold higher affinity
than CA11. Furthermore, RA07 inhibited IL-6-dependent KT-3 cell proliferation in a dose-dependent manner. ELISAs revealed
that RA07 could not inhibit IL-6 from binding to the IL-6 receptor (IL-6R), but could inhibit the IL-6/IL-6 complex binding
to gp130. |
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