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

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...

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Main Author: Johnson, Litty
Format: Thesis (University of Nottingham only)
Language:English
Published: 2019
Subjects:
Online Access:https://eprints.nottingham.ac.uk/56035/
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author Johnson, Litty
author_facet Johnson, Litty
author_sort Johnson, Litty
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-560352025-02-28T14:23:14Z https://eprints.nottingham.ac.uk/56035/ Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition Johnson, Litty 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. 2019-03-15 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/56035/1/Final%20Thesis%20%28e%20thesis%20submission%29.pdf Johnson, Litty (2019) Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition. MRes thesis, University of Nottingham. gel nucleoside gelator protein aggregation inhibition protein therapeutics
spellingShingle gel
nucleoside gelator
protein aggregation inhibition
protein therapeutics
Johnson, Litty
Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title_full Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title_fullStr Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title_full_unstemmed Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title_short Low molecular weight nucleoside gelator: A novel approach for protein and peptide aggregation inhibition
title_sort low molecular weight nucleoside gelator: a novel approach for protein and peptide aggregation inhibition
topic gel
nucleoside gelator
protein aggregation inhibition
protein therapeutics
url https://eprints.nottingham.ac.uk/56035/