Synthesis and functionalisation of defined molecular weight poly(ethylene glycol) and its application as a new class of PEGylation agents
File(s)
Author(s)
Burggraef, Maria Johanna
Type
Thesis
Abstract
The polymer poly(ethylene glycol) (PEG) is a highly hydrophilic polymer which is widely used in the pharmaceutical industry to mask therapeutics and that way increase their blood-residence time and decrease their immunogenicity.1 The technique of covalently binding one or more PEG units to a therapeutic is referred to as PEGylation and as of 2023, there were 40 FDA or EMA-approved PEGylated therapeutics on the market, most of which were proteins. The mass of the used PEG ranges from <1 kDa to 60 kDa and it is conventionally synthesised through the anionic polymerisation of ethylene oxide 2, which results in a Gaussian distribution of PEG of different chain lengths. This inherent dispersity creates problems with the characterisation of the PEGylation agents, as well as the PEGylated products, resulting in unidentified impurities or batch-to-batch variations. The disperse nature of the PEG makes it difficult to locate the exact PEGylation sites but identifying them is valuable for predicting potential interactions of the PEG with the active site of a therapeutic.
Version
Open Access
Date Issued
2023-12-27
Date Awarded
2024-05-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Livingston, Andrew G.
Sponsor
European Research Council
Grant Number
786398- EXACTYMER
Publisher Department
Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)