Protein Design and Engineering
A designed glycoprotein analogue of Gc-MAF exhibits native-like phagocytic activity.
Federica Bogani, Elizabeth McConnell, Lokesh Joshi, Yung Chang, and Giovanna Ghirlanda* [Arizona State Univ.]
J. Am. Chem. Soc.128, 7142 -7143 (2006)
De novo protein engineering is used to develop a mini-protein analogue of Gc-MAF, a glycoprotein involved in the immune system activation that showed anticancer activity in mice. Molecular modeling tools are used in conjunction with structural analysis to splice the glycosylated loop onto a stable three-helix bundle. The resulting 69-residue model peptide, MM1, is synthesized by solid-phase synthesis both in the aglycosylated and the glycosylated (GalNAc-MM1) form. GalNAc-MM1 provides a framework for the development of mutants with increased activity that is used in place of Gc-MAF as an immunomodulatory agent in therapy.
MMCC Results Volume 15 No. 2 1 June 2006