Abstract
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.
Highlights
Expanded radius of gyration slow down renal filtration through the glomerular pores and, can extend plasma half-life by up to one
Data from size exclusion chromatography, dynamic light scattering, circular dichroism spectroscopy and quantification of hydrodynamic and polar properties demonstrate that the biosynthetic proline/alanine-rich sequences (PAS) polypeptides exhibit random coil behavior in aqueous solution astonishingly similar to the chemical polymer poly-ethylene glycol (PEG)
PASylation technology was devised on the basis of a repetitive sequence comprising Pro, Ala and Ser residues.[9]
Summary
Expanded radius of gyration slow down renal filtration through the glomerular pores and, can extend plasma half-life by up to one.
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