title: High affinity type I interleukin 1 receptor antagonists discovered by screening recombinant peptide libraries.
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.
authors.affiliation: Department of Molecular Pharmacology, Affymax Research Institute, Palo Alto, CA 94304, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Yanofsky
authors.forename: D N
authors.initials: DN
authors.lastname: Baldwin
authors.forename: J H
authors.initials: JH
authors.lastname: Butler
authors.forename: F R
authors.initials: FR
authors.lastname: Holden
authors.forename: J W
authors.initials: JW
authors.lastname: Jacobs
authors.forename: P
authors.initials: P
authors.lastname: Balasubramanian
authors.forename: J P
authors.initials: JP
authors.lastname: Chinn
authors.forename: S E
authors.initials: SE
authors.lastname: Cwirla
authors.forename: E
authors.initials: E
authors.lastname: Peters-Bhatt
authors.forename: E A
authors.initials: EA
authors.lastname: Whitehorn
authors.forename: E H
authors.initials: EH
authors.lastname: Tate
authors.forename: A
authors.initials: A
authors.lastname: Akeson
authors.forename: T L
authors.initials: TL
authors.lastname: Bowlin
authors.forename: W J
authors.initials: WJ
authors.lastname: Dower
authors.forename: R W
authors.initials: RW
authors.lastname: Barrett
mesh_terms: D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D016208:Databases, Factual; D015232:Dinoprostone / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis; D004926:Escherichia coli; D000882:Haplorhini; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011869:Radioligand Assay; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D017931:DNA Primers; D007375:Interleukin-1; D010455:Peptides; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors; D015232:Dinoprostone