Schmoldt Hans-Ulrich, Daneschdar Matin, Kolmar Harald, Blind Michael
NascaCell Technologies AG, Munich, Germany.
Methods Mol Biol. 2009;535:361-72. doi: 10.1007/978-1-59745-557-2_20.
Microbodies are novel pharmacophoric entities which are derived from naturally occurring cystine-knot microproteins. They provide extremely stable scaffolds that can be engineered to high-affinity binding proteins. A peptide-grafting approach yielded specific ligands for human thrombopoietin receptor (TPO-R). Thrombopoietin (TPO) is the primary regulator of platelet production and acts by dimerization of its cognate receptor. Chemical cross linking of two anti TPO-R Microbodies resulted in highly potent TPO mimetics which are promising candidates for the treatment of TPO deficiencies. The approach demonstrates the high potential of dimeric Microbodies as synthetic receptor agonists.
微体是源自天然存在的胱氨酸结微蛋白的新型药效基团实体。它们提供了极其稳定的支架，可被设计成高亲和力结合蛋白。一种肽嫁接方法产生了针对人血小板生成素受体（TPO-R）的特异性配体。血小板生成素（TPO）是血小板生成的主要调节因子，通过其二聚化同源受体发挥作用。两种抗TPO-R微体的化学交联产生了高效的TPO模拟物，它们是治疗TPO缺乏症的有前景的候选药物。该方法证明了二聚体微体作为合成受体激动剂的巨大潜力。
