Yanofsky S D, Baldwin D N, Butler J H, Holden F R, Jacobs J W, Balasubramanian P, Chinn J P, Cwirla S E, Peters-Bhatt E, Whitehorn E A, Tate E H, Akeson A, Bowlin T L, Dower W J, Barrett R W
Department of Molecular Pharmacology, Affymax Research Institute, Palo Alto, CA 94304, USA.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7381-6. doi: 10.1073/pnas.93.14.7381.
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.
从重组肽展示文库中鉴定出了两类能特异性结合人I型白细胞介素I（IL-1）受体胞外域的肽。其中一个家族的肽可阻断IL-1α与I型IL-1受体的结合，IC50值为45 - 140微摩尔。对这些肽的变体进行亲和选择筛选，产生了亲和力高得多的配体（IC50约为2纳摩尔）。这些肽可阻断人和猴细胞中IL-1驱动的反应；它们不与人II型IL-1受体或鼠I型IL-1受体结合。这是（据我们所知）第一个与细胞因子受体结合并作为细胞因子拮抗剂的高亲和力肽的例子。
