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| Main Authors: | , , , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2025
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| Subjects: | |
| Online Access: | https://onlinelibrary.wiley.com/doi/10.1002/psc.70041 |
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Table of Contents:
- Chemical Synthesis of Medin via a Removable Aggregation‐Suppressing Linker Matthias De Vleeschouwer Brajabandhu Pradhan Frederic Rousseau Joost Schymkowitz Journal of Peptide Science ABSTRACTMedin, a 50‐amino acid fragment derived from the protein MFG‐E8 (lactadherin), is the most prevalent amyloid found in humans, present in the vasculature of nearly all individuals over the age of 50. Its biological relevance is highlighted by its co‐localization with amyloid‐β (Aβ) deposits in both Alzheimer's disease patients and transgenic mice models. Notably, Medin promotes amyloid‐β aggregation, forming mixed fibrils with Aβ and enhancing its deposition in blood vessels. Here we report a new and efficient strategy to chemically access this compound. Our approach employs a solubilizing linker that not only ensures high solubility but also suppresses aggregation, allowing efficient purification of the product. The linker can be removed without a trace, after which the product behaves identically to wild‐type Medin and forms amyloid fibrils. The synthesis route allows opening up a new chemical space, including nonnatural modifications like biotinylation. Together with the control over the aggregation properties, this is a powerful tool for amyloid protein studies. 10.1002/psc.70041 http://onlinelibrary.wiley.com/termsAndConditions#vor