Branched PEG Polymer Chain Attachment to Human Interferon β-1a: An Effect on Pharmacokinetic Properties of a Therapeutic Protein
Linear PEGylation, the covalent attachment of a linear polyethylene glycol polymer, is known to increase the pharmacokinetic properties of a protein with minimal alterations to protein function. This study observes the difference between the PEGylation of a protein with a linear PEG polymer and a branched PEG polymer. Given two PEG polymers of identical mass, it has been observed that a system using a branched polymer-protein conjugate will increase protein efficacy more than a linear conjugate. Conventional experiments are limited to observations on a microscopic scale; the molecular dynamic simulation in this study observes interactions on an atomic scale for a more precise view of conformational and energetic properties such as stability and active site inhibition. Future implications are discussed. Data presented here can help design new strategies to improve future PEGylation applications for potentially therapeutic proteins. The results of this project will enhance the fundamental understanding of the functions and dynamics in conjugated protein systems. The simulations will also allow the prediction of optimal PEG chain length and structure that would maximize drug efficacy. Potentially, It will offer atomic level insight into the effect of PEGylation and provide a novel strategy for the characterization and optimization of PEGylated therapeutic biomolecules.
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