The polypeptide biophysics of proline/alanine-rich sequences (PAS): Recombinant biopolymers with PEG-like properties

Biopolymers. 2018 Jan;109(1):e23069. doi: 10.1002/bip.23069. Epub 2017 Oct 27.


PAS polypeptides comprise long repetitive sequences of the small L-amino acids proline, alanine and/or serine that were developed to expand the hydrodynamic volume of conjugated pharmaceuticals and prolong their plasma half-life by retarding kidney filtration. Here, we have characterized the polymer properties both of the free polypeptides and in fusion with the biopharmaceutical IL-1Ra. Data from size exclusion chromatography, dynamic light scattering, circular dichroism spectroscopy and quantification of hydrodynamic and polar properties demonstrate that the biosynthetic PAS polypeptides exhibit random coil behavior in aqueous solution astonishingly similar to the chemical polymer poly-ethylene glycol (PEG). The solvent-exposed PAS peptide groups, in the absence of secondary structure, account for strong hydrophilicity, with negligible contribution by the Ser side chains. Notably, PAS polypeptides exceed PEG of comparable molecular mass in hydrophilicity and hydrodynamic volume while exhibiting lower viscosity. Their uniform monodisperse composition as genetically encoded polymers and their biological nature, offering biodegradability, render PAS polypeptides a promising PEG mimetic for biopharmaceutical applications.

Keywords: PASylation; biomimetics; hydrodynamic volume; recombinant polypeptide; viscosity.

MeSH terms

  • Humans
  • Interleukin 1 Receptor Antagonist Protein / chemistry*
  • Polyethylene Glycols*
  • Recombinant Fusion Proteins / chemistry*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Recombinant Fusion Proteins
  • Polyethylene Glycols