Prikalkhoran, S;
Guiliano, D;
Khalili, H;
(2024)
Storage stability and solution binding affinity of an Fc-fusion mimetic.
Journal of Pharmaceutical Sciences
10.1016/j.xphs.2024.11.016.
(In press).
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Abstract
This study evaluates the storage stability and solution binding affinity of a novel Fc-fusion mimetic, receptor-PEG-receptor (RpR), designed to address limitations of the current therapeutic aflibercept, a gold-standard therapy for age-macular degeneration (AMD). Using di(bis-sulfone) PEG linker as a structural scaffold, the mimetic aims to improve the storage stability and binding efficacy of the Fc fusion protein. Mass photometry and size-exclusion chromatography demonstrated that RpR, even in an unformulated buffer, exhibits superior storage stability exceeding 10 months compared to aflibercept. Furthermore, microscale thermophoresis was employed to determine RpR's binding affinity to VEGF in solution, providing a more physiologically relevant assessment than traditional binding assays. These findings highlight RpR's potential as a therapeutic candidate for the treatment of AMD disease, warranting further investigation.
| Type: | Article |
|---|---|
| Title: | Storage stability and solution binding affinity of an Fc-fusion mimetic |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.xphs.2024.11.016 |
| Publisher version: | https://doi.org/10.1016/j.xphs.2024.11.016 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Aflibercept, Binding affinity, Bis-alkylation, Fc-fusion mimetic, MST, Protein therapeutics, Solution stability |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10203561 |
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