Diffusion of small molecule drugs is affected by surface interactions and crowder proteins
Crowded environments are known to affect the diffusion of macromolecules, but their effects on the diffusion of small molecules are largely uncharacterized. We investigate how three protein crowders, bovine serum albumin (BSA), hen egg-white lysozyme, and myoglobin, influence the diffusion rates and...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 September 2022
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| In: |
iScience
Year: 2022, Volume: 25, Issue: 10, Pages: 1-24 |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2022.105088 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.isci.2022.105088 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004222013608 
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| Author Notes: | Debabrata Dey, Ariane Nunes-Alves, Rebecca C. Wade, and Gideon Schreiber |
| Summary: | Crowded environments are known to affect the diffusion of macromolecules, but their effects on the diffusion of small molecules are largely uncharacterized. We investigate how three protein crowders, bovine serum albumin (BSA), hen egg-white lysozyme, and myoglobin, influence the diffusion rates and interactions of four small molecules: fluorescein, and three drugs, doxorubicin, glycogen synthase kinase-3 inhibitor SB216763, and quinacrine. Using Line-FRAP measurements, Brownian dynamics simulations, and molecular docking, we find that the diffusion rates of the small molecules are highly affected by self-aggregation, interactions with the proteins, and surface adsorption. The diffusion of fluorescein is decreased because of its interactions with the protein crowders and their surface adsorption. Protein crowders increase the diffusion rates of doxorubicin and SB216763 by reducing surface interactions and self-aggregation, respectively. Quinacrine diffusion was not affected by protein crowders. The mechanistic insights gained here may assist in optimization of compounds for higher mobility in complex macromolecular environments. |
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| Item Description: | Online verfügbar 7 September 2022, Artikelversion 16 September 2022 Gesehen am 19.01.2023 |
| Physical Description: | Online Resource |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2022.105088 |