Microbodies.
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.
Schmoldt
Hans-Ulrich
HU
NascaCell Technologies AG, Munich, Germany.
Daneschdar
Matin
M
Kolmar
Harald
H
Blind
Michael
M
D000595:Amino Acid Sequence; D032701:Biomimetics; D002460:Cell Line; D049109:Cell Proliferation; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010957:Plasmids; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D055503:Protein Multimerization; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000378:metabolism*
D008024:Ligands; D010455:Peptides; D053628:Receptors, Thrombopoietin; D003545:Cysteine