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Dognini, P, Chaudhry, T, Scagnetti, G, Assante, M, Hanson, GSM, Ross, K, Giuntini, F and Coxon, CR (2023) 5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin as Functional Platform for Peptide Stapling and Multicyclisation. Chemistry (Weinheim an der Bergstrasse, Germany). e202301410. ISSN 0947-6539
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5,10,15,20-Tetrakis(pentafluorophenyl)porphyrin as Functional Platform for Peptide Stapling and Multicyclisation.pdf - Published Version Available under License Creative Commons Attribution. Download (5MB) | Preview |
Abstract
Polyfluorinated aromatic reagents readily react with thiolates via nucleophilic aromatic substitution (SNAr) and provide excellent scaffolds for peptide cyclisation. Here we report a robust and versatile platform for peptide stapling and multicyclisation templated by 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, opening the door to the next generation of functional scaffolds for 3D peptide architectures. We demonstrate that stapling and multicyclisation occurs with a range of non-protected peptides under peptide-compatible conditions, exhibiting chemoselectivity and wide-applicability. Peptides containing two cysteine residues are readily stapled, and the remaining perfluoroaryl groups permit the introduction of a second peptide in a modular fashion to access bicyclic peptides. Similarly, peptides with more than two cysteine residues can afford multicyclic products containing up to three peptide 'loops'. Finally, we demonstrate that a porphyrin-templated stapled peptide containing the Skin Penetrating and Cell Entering (SPACE) peptide affords a skin cell penetrating conjugate with intrinsic fluorescence.
| Item Type: | Article |
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| Uncontrolled Keywords: | Bioconjugation; SNAr; cyclic peptides; fluorine; strapped porphyrins; 03 Chemical Sciences; General Chemistry |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Wiley |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 07 Jul 2023 10:28 |
| Last Modified: | 20 Sep 2023 16:00 |
| DOI or ID number: | 10.1002/chem.202301410 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/20269 |
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