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.
