Chief Technology Officer, XL-protein GmbH
Prospects of PASylation® for the design of protein and peptide therapeutics with extended half-life and enhanced action
PASylation® technology comprises the conjugation – via genetic fusion or chemical coupling – of peptides, proteins and small molecule drugs, with natively disordered biosynthetic polypeptides made of the small L-amino acids Pro, Ala and/or Ser. Such proline/alanine-rich sequences (PAS) are highly soluble in physiological solution and stably adopt random coil conformation. This results in an expanded hydrodynamic volume, leading to retarded kidney filtration and drastically prolonged pharmacokinetics in vivo. The intrinsically uncharged PAS polypeptides do not interfere with the pharmacological activity of the drug component and show high stability in plasma as well as no immunogenicity. Furthermore, PAS sequences undergo quick degradation and metabolization after cellular uptake, thus avoiding side effects such as organ accumulation or vacuolation typically seen for several PEGylated products. PASylation is compatible with bacterial, yeast as well as mammalian expression systems and allows a cheap, one-step production of the PAS-fusion protein/peptide without the need of costly chemical modification steps. This presentation will focus on fundamental concepts of PASylation and will highlight recent advances in preclinical applications.
Uli Binder is Co-founder of XL-protein GmbH and acts as Chief Technology Officer of the company since it’s since its inception in 2009. He studied Molecular Biotechnology and accomplished his Ph.D. studies at the Technical University of Munich in the field of protein engineering.