Monobody

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Monobodies , also called adnectins , are artificial proteins that are capable of binding antigens . Although her name a kinship to antibodies (Engl. Antibody ) suggests they are not structurally of immunoglobulins , but from fibronectin derived. Monobodies consist of 94 amino acids and, with a molecular mass of about 10  kDa, are about 15 times smaller than antibodies of the IgG type. Monobodies are largely developed by the biotech company Adnexus , which has been part of Bristol-Myers Squibb since 2007 . The MonoBody Pegdinetanib (CT-322, Angiocept), a VEGF - receptor - antagonist , is currently in the second phase of clinical development for the treatment of glioblastoma and other cancers .

structure

Monobodies are derived from human fibronectin, more precisely from the tenth type III extracellular fibronectin domain. This domain has an immunoglobulin-like β-sheet structure with 3 exposed loops per side. Modifications in the loops BC and FG of the fibronectin domains lead to monobodies with differing protein recognition patterns. Metal ion binding sites and the central disulfide bridge are missing in the structure of the monobodies.

Individual evidence

  1. a b Koide A, Koide S: Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain . In: . Methods Mol Biol. . 352, 2007, pp. 95-109. PMID 17041261 .
  2. Bloom L, Calabro V: FN3: a new protein scaffold reaches the clinic . In: Drug Discov Today . July 2009. doi : 10.1016 / j.drudis.2009.06.007 . PMID 19576999 .
  3. Koide A, Bailey CW, Huang X, Koide S: The fibronectin type III domain as a scaffold for novel binding proteins . In: J. Mol. Biol. . 284, No. 4, December 1998, pp. 1141-51. doi : 10.1006 / jmbi.1998.2238 . PMID 9837732 .