Jump to main content
Jump to site search

Issue 5, 2018, Issue in Progress
Previous Article Next Article

Molecular insights into the improved clinical performance of PEGylated interferon therapeutics: a molecular dynamics perspective

Author affiliations

Abstract

PEGylation is a widely adopted process to covalently attach a polyethylene glycol (PEG) polymer to a protein drug for the purpose of optimizing drug clinical performance. While the outcomes of PEGylation in imparting pharmacological advantages have been examined through experimental studies, the underlying molecular mechanisms remain poorly understood. Using interferon (IFN) as a representative model system, we carried out comparative molecular dynamics (MD) simulations of free PEGx, apo-IFN, and PEGx-IFN (x = 50, 100, 200, 300) to characterize the molecular-level changes in IFN introduced by PEGylation. The simulations yielded molecular evidence directly linked to the improved protein stability, bioavailability, retention time, as well as the decrease in protein bioactivity with PEG conjugates. Our results indicate that there is a tradeoff between the benefits and costs of PEGylation. The optimal PEG chain length used in PEGylation needs to strike a good balance among the competing factors and maximizes the overall therapeutic efficacy of the protein drug. We anticipate the study will have a broad implication for protein drug design and development, and provide a unique computational approach in the context of optimizing PEGylated protein drug conjugates.

Graphical abstract: Molecular insights into the improved clinical performance of PEGylated interferon therapeutics: a molecular dynamics perspective

Back to tab navigation

Supplementary files

Article information


Submitted
15 Nov 2017
Accepted
03 Jan 2018
First published
09 Jan 2018

This article is Open Access

RSC Adv., 2018,8, 2315-2322
Article type
Paper

Molecular insights into the improved clinical performance of PEGylated interferon therapeutics: a molecular dynamics perspective

D. Xu, N. Smolin, R. K. Shaw, S. R. Battey, A. Tao, Y. Huang, S. E. Rahman and Matthew L. Caylor, RSC Adv., 2018, 8, 2315
DOI: 10.1039/C7RA12480E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements