Small molecule modulation of protein polymerization
The modulation of protein surface physicochemistry through single point mutations can trigger polymerization, which is facilitated by subunit repetition within a homomeric complex. Furthermore, monogenic disorders may result from aberrant supramolecular assemblies caused by missense mutations that modify the protein surface. Noteworthy from a therapeutic perspective, small molecules have been shown to not only mediate and enhance polymerization, analogous to a surface residue perturbation, but also bind and stabilize the repeating unit to inhibit the self-assembly event. We exemplify pharmacological manipulation of polymeric protein assemblies using some recently reported studies. The aim of this Viewpoint is to highlight opportunities to rationally control protein polymerization for therapeutic benefit.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
Chemical Society reviews - 51(2022), 7 vom: 04. Apr., Seite 2392-2396 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fischer, Eric S [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 05.04.2022 Date Revised 05.04.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d2cs00070a |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM337973563 |
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| 520 | |a The modulation of protein surface physicochemistry through single point mutations can trigger polymerization, which is facilitated by subunit repetition within a homomeric complex. Furthermore, monogenic disorders may result from aberrant supramolecular assemblies caused by missense mutations that modify the protein surface. Noteworthy from a therapeutic perspective, small molecules have been shown to not only mediate and enhance polymerization, analogous to a surface residue perturbation, but also bind and stabilize the repeating unit to inhibit the self-assembly event. We exemplify pharmacological manipulation of polymeric protein assemblies using some recently reported studies. The aim of this Viewpoint is to highlight opportunities to rationally control protein polymerization for therapeutic benefit | ||
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