文章基本信息

标题：Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks
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作者：Lauge Schäffer ; Renee E. Brissette ; Jane C. Spetzler 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：8
页码：4435-4439
DOI：10.1073/pnas.0830026100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Insulin is thought to elicit its effects by crosslinking the two extracellular -subunits of its receptor, thereby inducing a conformational change in the receptor, which activates the intracellular tyrosine kinase signaling cascade. Previously we identified a series of peptides binding to two discrete hotspots on the insulin receptor. Here we show that covalent linkage of such peptides into homodimers or heterodimers results in insulin agonists or antagonists, depending on how the peptides are linked. An optimized agonist has been shown, both in vitro and in vivo, to have a potency close to that of insulin itself. The ability to construct such peptide derivatives may offer a path for developing agonists or antagonists for treatment of a wide variety of diseases.