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Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7381-6.

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

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Department of Molecular Pharmacology, Affymax Research Institute, Palo Alto, CA 94304, USA.


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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