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PASylation enhances the stability, potency, and plasma half-life of interferon α-2a: A molecular dynamics simulation

Shamloo, A ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1002/biot.201900385
  3. Publisher: Wiley-VCH Verlag , 2020
  4. Abstract:
  5. In this study, the effectiveness of PASylation in enhancing the potency and plasma half-life of pharmaceutical proteins has been accredited as an alternative technique to the conventional methods such as PEGylation. Proline, alanine, and serine (PAS) chain has shown some advantages including biodegradability improvement and plasma half-life enhancement while lacking immunogenicity or toxicity. Although some experimental studies have been performed to find the mechanism behind PASylation, the detailed mechanism of PAS effects on the pharmaceutical proteins has remained obscure, especially at the molecular level. In this study, the interaction of interferon α-2a (IFN) and PAS chain is investigated using molecular dynamics simulation method. Several important parameters including secondary structure, root-mean-square distance, and solvent accessible surface area to investigate the stability, bioavailability, and bioactivity of the PASylated protein are studied. The results demonstrate that IFN conformation is not affected critically through PASylation while it results in improvement of the protein stability and bioactivity. Therefore, PASylation can be considered as a proper biological alternative technique to increase the plasma half-life of the biopharmaceutical proteins through enlarging apparent volume. The proposed simulation represents a computational approach that would provide a basis for the study of PASylated pharmaceutical proteins for different future applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
  6. Keywords:
  7. Interferon α-2a ; PASylation ; Plasma half-life ; Protein therapeutics ; Amino acids ; Antibiotics ; Biochemistry ; Biodegradability ; Glycoproteins ; Plasma stability ; Proteins ; Biopharmaceutical proteins ; Computational approach ; Molecular dynamics simulation methods ; Molecular dynamics simulations ; Pharmaceutical protein ; Root-mean-square distances ; Secondary structures ; Solvent accessible surface areas ; Molecular dynamics ; Alanine ; Alpha2a interferon ; Proline ; Serine ; Chemical modification ; Drug bioavailability ; Drug potency ; Drug stability ; Drug structure ; Plasma half life ; Priority journal ; Protein conformation ; Statistical analysis ; Surface area
  8. Source: Biotechnology Journal ; Volume 15, Issue 8 , 2020
  9. URL: https://onlinelibrary.wiley.com/doi/full/10.1002/biot.201900385