Thursday, October 18, 2012
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properties of protein therapeutics through peptide extensions that interact
with the Fc
fragment of IgG receptor transporter-a (FCGRT;
Peptide extensions that
promote the interaction of proteins with FCRN could improve the drug-like
properties of protein therapeutics. Some protein therapeutics are conjugated
to the Fc domain of IgG, which interacts with FCRN, to increase plasma
half-life, but the large size of the resulting fusion protein can interfere
with tissue penetration and biological activity. In a proof-of-principle
experiment, short peptide sequences that compete with IgG for binding to FCRN
were conjugated to the N-terminal and/or C-terminal ends of a fluorescent
protein. In cell culture, the peptide-based fusion proteins were internalized
and transcytosed across a cell monolayer, which is similar to what is seen
with IgG fusions. Next steps include testing peptide-modified protein
therapeutics in animal models.
Published online Oct. 18, 2012
Patent application filed;
available for licensing
Sockolosky, J.T. et al.
Proc. Natl. Acad. Sci. USA; Sept. 18, 2012;
Contact: Francis C. Szoka, University of California, San
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