PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins

• Published in: Protein engineering, design and selection Vol. 26; no. 8; pp. 489 - 501
• Main Authors: Schlapschy, Martin, Binder, Uli, Börger, Claudia, Theobald, Ina, Wachinger, Klaus, Kisling, Sigrid, Haller, Dirk, Skerra, Arne
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2013
• Subjects: Alanine - chemistry; Alanine - genetics; Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; Drugs; Escherichia coli - genetics; Growth Hormone - chemistry; Growth Hormone - genetics; Growth Hormone - pharmacokinetics; Half-Life; Humans; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - genetics; Mice; Models, Molecular; Molecular Sequence Data; Original; Peptides - chemistry; Peptides - genetics; Polyethylene Glycols - chemistry; Proline - chemistry; Proline - genetics; Protein Structure, Secondary; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacokinetics; Serine - chemistry; Serine - genetics; pharmacokinetics; therapeutic protein; kidney filtration; dosing; biologic

A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration, which strongly hampers efficacy both in animal studies and in human therapy. We have developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising...