Development of a Fast Screening Method for Selecting Excipients in Formulations using MD simulations, NMR and MicroScale Thermophoresis
| Autor: | Werner Streicher, Christin Pohl, Alexander P. Golovanov, Pernille Harris, Matja Zalar, Sowmya Indrakumar, Nuska Tschammer, Allan Nørgaard, Günther H.J. Peters |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug Compounding
Proton Magnetic Resonance Spectroscopy Pharmaceutical Science Excipient Peptide 02 engineering and technology Molecular Dynamics Simulation Infections 030226 pharmacology & pharmacy Excipients 03 medical and health sciences Molecular dynamics 0302 clinical medicine Molecular level Anti-Infective Agents Nmr titration medicine Screening method Humans chemistry.chemical_classification Microscale thermophoresis Reproducibility of Results General Medicine Plectasin 021001 nanoscience & nanotechnology Combinatorial chemistry High-Throughput Screening Assays chemistry Peptides 0210 nano-technology Biotechnology medicine.drug |
| Zdroj: | Indrakumar, S, Zalar, M, Tschammer, N, Pohl, C A, Nørgaard, A, Streicher, W, Harris, P, Golovanov, A P & Peters, G H J 2021, ' Development of a Fast Screening Method for Selecting Excipients in Formulations using MD simulations, NMR and MicroScale Thermophoresis ', European Journal of Pharmaceutics and Biopharmaceutics, vol. 158, pp. 11-20 . https://doi.org/10.1016/j.ejpb.2020.10.015 |
| DOI: | 10.1016/j.ejpb.2020.10.015 |
| Popis: | Development of peptide therapeutics generally involves screening of excipients that inhibit peptide-peptide interactions, hence aggregation, and improve peptide stability. We used the therapeutic peptide plectasin to develop a fast screening method that combines microscale thermophoresis titration assays and molecular dynamics simulations to relatively rank the excipients with respect to binding affinity and to study key peptide-excipient interaction hotspots on a molecular level, respectively. Additionally, 1H-13C-HSQC NMR titration experiments were performed to validate the fast screening approach. The NMR results are in qualitative agreement with results from the fast screening method demonstrating that this approach can be reliably applied to other peptides and proteins as a fast screening method to relatively rank excipients and predict possible excipient binding sites. |
| Databáze: | OpenAIRE |
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