Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition

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Johnson, Litty (2019) Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition. MRes thesis, University of Nottingham.

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Abstract

Protein and peptide based therapeutics have become one of the most rapidly growing class of therapeutics that have potential to treat human disease. However, their inherent instability limits their application, which in turn minimises their therapeutic potential. Among all the physical and chemical instabilities, protein aggregation has become the major important cause of concern in the biopharmaceutical industry. Several additives are currently employed to prevent this. However, these additives possess several drawbacks such as their ability to denature proteins. Thus, there is a need to develop a novel method for the prevention of aggregation that could extend the shelf life of these biotherapeutics.

Low molecular weight nucleoside gelators have been widely used as a candidate for the delivery of biologics due to their excellent biocompatibility. However, their influence on the inhibition of protein aggregation has not been studied. Herein, we are reporting the ability of the nucleoside gelator, N4-octanoyl-2ʹ-deoxycytidine to inhibit protein aggregation.

Using turbidimetric, spectroscopic and microscopy methods, we have demonstrated that inhibition of protein aggregation is dependent on gelator concentration. Moreover the model proteins were found to be functionally active in the hydrogel system. All our results revealed that this gelator exhibited the ability to suppress aggregation of proteins with a broad range of isoelectric points. Thus, the 2ʹ deoxycytidine based hydrogel has potential in tackling one of the most important challenges in the formulation of biologics i.e.protein aggregation.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Marlow, Maria
Zelzer, Mischa
Allen, Stephanie
Keywords: gel, nucleoside gelator, protein aggregation inhibition, protein therapeutics
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 56035
Depositing User: JOHNSON, LITTY
Date Deposited: 13 Sep 2023 10:45
Last Modified: 13 Sep 2023 10:45
URI: https://eprints.nottingham.ac.uk/id/eprint/56035

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