Conference Proceeding

The effect of polysulfide-conjugation on the stability and activity of lysozyme

Ms. Farah El Mohtadi,
The University of Manchester, United kingdom

Enzyme replacement therapies (ERT) are used to treat lysosomal storage diseases (LSDs) and are some of the most expensive treatments available today. Examples of LSDs include Gaucher’s disease (GD), Hunter’s disease and Fabry’s disease (FD).

Farah El Mohtadi is a Ph.D. student in Manchester Pharmacy School, at The University of Manchester. She is working under the supervision of Prof Nicola Tirelli and Prof Ian Stratford. She obtained my master’s degree in Pharmaceutical Technology from Jordan University of Science and Technology, and she joined the University of Manchester in 2013. Her research currently focuses on the development and characterisation of novel polymers and their conjugation to proteins.

Enzyme replacement therapies (ERT) are used to treat lysosomal storage diseases (LSDs) and are some of the most expensive treatments available today. Examples of LSDs include Gaucher’s disease (GD), Hunter’s disease and Fabry’s disease (FD). GD is the most common of the LSD caused by the deficiency of glucocerebrosidase, a lysosomal enzyme those catalyses the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Current therapy relies on a bi-weekly injection of an exogenous glucosidase which costs approximately US$150,000 – 300,000 per year, making it one of the most expensive treatments on the market. Efforts to improve the stability of the enzyme may therefore result in considerably benefits both clinically for the patients and financially for the insurance companies/care providers. It has been found that oxidation can be a significant factor in reducing the activity of beta-glucosidase in those with GD. Moreover, in FD it has been found that anti-body formation to the exogenous enzyme can play a significant role in reducing the available enzyme as well as causing significant immunogenic side-effects. Herein we describe a polymer-enzyme conjugate where we use polysulfide an anti-oxidant polymer and lysozyme as a model enzyme. SDS-PAGE together with MALDI-TOF analysis revealed conjugation of 1 – 3 polysulfide chains per lysozyme with only a slightly reduction in lysozyme activity. Unlike the native lysozyme, the lysozyme-polysulfide conjugate was found to be resistant to oxidative denaturation and had reduced binding to lysozyme antibodies (indicating a lower immunogenicity).

Published: 27 April 2017