A novel hGM-CSF-derived peptide to generate highly O-glycosylated hIFN-alfa2b variants

FERRANDO, V.; OGGERO, M.; ETCHEVERRIGARAY, M.; KRATJE, R.; CEAGLIO, N.

Villa General Belgrano, Córdoba

Simposio; 2nd Argentinian Symposium of Glycobiology; 2016

CIQUIBIC-Instituto Leloir-IBYME- CONICET-Sociedad Latinoamericana de Glicobiología

Currently, the clinical use of therapeutic recombinant proteins presents certain limitations because of problems such as low stability and short half-life. Different strategies of glycoengineering have been widely used for the modification of properties such as stability, solubility, bioactivity, half-life and immunogenicity of recombinant therapeutic proteins. In particular, the fusion of peptides capable of incorporating O‑glycans into human proteins of pharmacological interest has been successfully carried out. The strategy implemented in this work was the fusion to a novel peptide (GMOPm) derived from the human granulocyte and macrophage colony-stimulating factor (hGM‑CSF) to produce highly O‑glycosylated human IFN-α2b variants. GMOPm is constituted by the first 7 amino acids from the N-terminal region of hGM-CSF plus 8 residues that have been modified in order to have a total of 6 sites susceptible of O‑glycosylation. In addition, a linear epitope comprising the first 4 amino acids of this peptide which is recognized by a mAb developed in our lab (CC1H7) has been identified. Our goal was to design and produce chimeric therapeutic proteins incorporating the novel peptide tag GMOPm to obtain molecules with improved properties such as stability, half-life and, consequently, bioactivity, due to the incorporation of O-glycans.