Improving Fmoc Solid Phase Synthesis of Human Beta Defensin 3
| Autor: | Aleksandra Walewska, Paulina Kosikowska-Adamus, Marta Tomczykowska, Bartosz Jaroszewski, Adam Prahl, Grzegorz Bulaj |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
beta-Defensins
Organic Chemistry General Medicine Dipeptides Ligands Catalysis Computer Science Applications Inorganic Chemistry Potassium Channels Voltage-Gated fmoc solid phase synthesis cys residue protecting groups pseudoproline dipeptides disulfide bond human beta defensin 3 selenocysteine Humans Amino Acid Sequence Disulfides Physical and Theoretical Chemistry Receptors Cytokine Peptides Molecular Biology Spectroscopy Solid-Phase Synthesis Techniques |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12562 |
| ISSN: | 1422-0067 |
| Popis: | Human β-defensin 3, HBD-3, is a 45-residue antimicrobial and immunomodulatory peptide that plays multiple roles in the host defense system. In addition to interacting with cell membranes, HBD-3 is also a ligand for melanocortin receptors, cytokine receptors and voltage-gated potassium channels. Structural and functional studies of HBD-3 have been hampered by inefficient synthetic and recombinant expression methods. Herein, we report an optimized Fmoc solid-phase synthesis of this peptide using an orthogonal disulfide bonds formation strategy. Our results suggest that utilization of an optimized resin, coupling reagents and pseudoproline dipeptide building blocks decrease chain aggregation and largely improve the amount of the target peptide in the final crude material, making the synthesis more efficient. We also present an alternative synthesis of HBD-3 in which a replacement of a native disulfide bridge with a diselenide bond improved the oxidative folding. Our work enables further biological and pharmacological characterization of HBD-3, hence advancing our understanding of its therapeutic potential. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |