Academic Journal
Enhancement of Coiled-Coil Stability via Interhelical Click Chemistry Stapling.
| Τίτλος: | Enhancement of Coiled-Coil Stability via Interhelical Click Chemistry Stapling. |
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| Συγγραφείς: | Posey TJ; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware19716, United States., Blum JE; Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, Pennsylvania19104, United States., Meisenhelter JE; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware19716, United States., Rears WJ; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware19716, United States., Pochan DJ; Department of Materials Science and Engineering, University of Delaware, 201 P.S. duPont Hall, Newark, Delaware19716, United States., Saven JG; Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, Pennsylvania19104, United States., Kloxin CJ; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, Delaware19716, United States.; Department of Materials Science and Engineering, University of Delaware, 201 P.S. duPont Hall, Newark, Delaware19716, United States. |
| Πηγή: | Bioconjugate chemistry [Bioconjug Chem] 2026 Aug 19; Vol. 37 (8), pp. 1545-1550. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9010319 Publication Model: Print Cited Medium: Internet ISSN: 1520-4812 (Electronic) Linking ISSN: 10431802 NLM ISO Abbreviation: Bioconjug Chem Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Chemical Society, c1990- |
| Ιατρικοί όροι (MeSH): | Peptides*/chemistry , Peptides*/chemical synthesis , Click Chemistry*/methods, Cysteine/chemistry ; Protein Stability ; Protein Structure, Secondary ; Models, Molecular |
| Περίληψη: | Coiled coil peptide assemblies are useful scaffolds for biomolecular and materials design, but their function often depends on preserving the folded oligomeric state after chemical modification or exposure to demanding conditions. While many peptide-stapling strategies stabilize individual α-helices, approaches that covalently reinforce higher-order architectures remain less developed. Here, we introduce an "assemble-and-click" strategy for interhelical stapling of a designed tetramer coiled coil. Cysteine and vinyl sulfonamide handles were positioned at symmetry-related sites that are brought into proximity by coiled-coil assembly, enabling pH-triggered thiol-Michael coupling after tetramer formation. LC-MS supports rapid formation of covalently linked dimeric products, SEC-MALS indicates that the stapled peptide retains the expected tetrameric assembly state, and circular dichroism shows markedly enhanced thermal robustness, with no cooperative unfolding observed up to 90 °C under the conditions examined. This approach provides a chemically programmable route to reinforcing higher-order coiled coil assemblies while preserving their oligomeric architecture. (© 2026 The Authors. Published by American Chemical Society.) |
| Grant Information: | DE-SC0019282 Basic Energy Sciences; DE-SC0019355 Basic Energy Sciences; 1548562 National Science Foundation (NSF); 2137603 National Science Foundation (NSF); 2138259 National Science Foundation (NSF); 2138286 National Science Foundation (NSF); 2138296 National Science Foundation (NSF); 2138307 National Science Foundation (NSF); CHE-2404305 National Science Foundation (NSF); DMR-2011824 National Science Foundation (NSF); TG-CHE110041 National Science Foundation (NSF) |
| Substance Nomenclature: | 0 (Peptides) K848JZ4886 (Cysteine) |
| Entry Date(s): | Date Created: 20260819 Date Completed: 20260819 Latest Revision: 20260819 |
| Update Code: | 20260820 |
| DOI: | 10.1021/acs.bioconjchem.6c00270 |
| PMID: | 42615511 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1520-4812 |
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| DOI: | 10.1021/acs.bioconjchem.6c00270 |