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. 1996 Jul 9;93(14):7381–7386. doi: 10.1073/pnas.93.14.7381

High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries.

S D Yanofsky 1, D N Baldwin 1, J H Butler 1, F R Holden 1, J W Jacobs 1, P Balasubramanian 1, J P Chinn 1, S E Cwirla 1, E Peters-Bhatt 1, E A Whitehorn 1, E H Tate 1, A Akeson 1, T L Bowlin 1, W J Dower 1, R W Barrett 1
PMCID: PMC38993  PMID: 8693002

Abstract

Two families of peptides that specifically bind the extracellular domain of the human type I interleukin I (IL-1) receptor were identified from recombinant peptide display libraries. Peptides from one of these families blocked binding of IL-lalpha to the type I IL-1 receptor with IC50 values of 45-140 microM. Affinity-selective screening of variants of these peptides produced ligands of much higher affinity (IC50 approximately 2 nM). These peptides block IL-1-driven responses in human and monkey cells; they do not bind the human type II IL-1 receptor or the murine type I IL-1 receptor. This is the first example (that we know of) of a high affinity peptide that binds to a cytokine receptor and acts as a cytokine antagonist.

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Selected References

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