Academic Journal
Peptide Thioester and Triazole Derivatives Through On-Resin Dual-Modification of Peptide Thiosulfonates.
| Τίτλος: | Peptide Thioester and Triazole Derivatives Through On-Resin Dual-Modification of Peptide Thiosulfonates. |
|---|---|
| Συγγραφείς: | Werner M; Institute of Organic Chemistry, Heidelberg University, Heidelberg, Germany.; Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Heidelberg, Germany., Bergmann A; Institute of Organic Chemistry, Heidelberg University, Heidelberg, Germany., Liu C; Institute of Organic Chemistry, Heidelberg University, Heidelberg, Germany., Behnam M; Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Heidelberg, Germany., Klein C; Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, Heidelberg, Germany., Thomas F; Institute of Organic Chemistry, Heidelberg University, Heidelberg, Germany. |
| Πηγή: | Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2026 Sep 14; Vol. 65 (38), pp. e8315692. Date of Electronic Publication: 2026 Jul 13. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2004-> : Weinheim : Wiley-VCH Original Publication: Weinheim/Bergstr. : New York, : Verlag Chemie ; Academic Press, c1962- |
| Ιατρικοί όροι (MeSH): | Peptides*/chemistry , Peptides*/chemical synthesis , Triazoles*/chemistry , Esters*/chemistry , Sulfhydryl Compounds*/chemistry, Azides/chemistry ; Alkynes/chemistry ; Click Chemistry ; Molecular Structure ; Catalysis |
| Περίληψη: | Modified peptides are an important class of drugs due to their high specificity and affinity in particular to pharmacological targets that are not druggable by conventional small molecules. Methods that allow the efficient diversification of peptides with non-canonical modifications are therefore highly sought after. One possible strategy for accessing broadly diversified peptides is on-resin late-stage modification, whereby a functional site-typically an amino acid side chain or the N-terminus-is usually singly modified after peptide chain assembly, while the other functionalities remain protected. Here, we present an on-resin late-stage dual-modification approach. This approach involves a reaction sequence that includes copper-catalyzed S-alkynylation of a resin-bound peptide thiosulfonate, followed by an iridium-catalyzed azide-alkyne click reaction (IrAAC). Thus, peptides with complex non-canonical modifications are obtained. The dual-modification approach is highly modular and compatible with a wide range of alkynes for S-alkynylation and azides for IrAAC. Furthermore, this chemistry can be used to modify complex peptides, such as the 34-amino-acid WW domain. In a structure-activity relationship study of triazole-containing peptide protease inhibitors of the dengue virus, we demonstrate the great potential of the modular on-resin dual-modification of peptide thiosulfonates for modulating peptide-protein interactions. (© 2026 The Author(s). Angewandte Chemie International Edition published by Wiley‐VCH GmbH.) |
| References: | Bioorg Med Chem. 2018 Jun 1;26(10):2759-2765. (PMID: 29395804) ACS Med Chem Lett. 2023 Apr 24;14(5):557-565. (PMID: 37197469) Angew Chem Int Ed Engl. 2021 Aug 9;60(33):17963-17968. (PMID: 34038604) J Biomol Screen. 2009 Oct;14(9):1102-8. (PMID: 19726784) Org Lett. 2024 Aug 16;26(32):6798-6802. (PMID: 39109986) Org Biomol Chem. 2016 Oct 18;14(41):9695-9711. (PMID: 27714241) J Org Chem. 1970 Oct;35(10):3563-5. (PMID: 5507099) Nat Rev Drug Discov. 2017 Aug;16(8):565-586. (PMID: 28473729) Chem Rev. 2019 Jun 26;119(12):7328-7443. (PMID: 31050890) Angew Chem Int Ed Engl. 2015 May 4;54(19):5632-5. (PMID: 25784284) Science. 1994 Nov 4;266(5186):776-9. (PMID: 7973629) Cell. 1997 Jun 13;89(6):875-86. (PMID: 9200606) Chem Rev. 2008 Aug;108(8):2952-3015. (PMID: 18698735) Chemistry. 2022 Sep 6;28(50):e202201339. (PMID: 35700354) Nat Rev Drug Discov. 2021 Apr;20(4):309-325. (PMID: 33536635) Antiviral Res. 2025 Feb;234:106053. (PMID: 39645089) Biochimie. 2024 Dec;227(Pt A):15-27. (PMID: 38871044) Cell Rep. 2020 Jul 14;32(2):107885. (PMID: 32668259) Expert Opin Drug Discov. 2019 Aug;14(8):779-789. (PMID: 31094231) Chem Commun (Camb). 2022 May 24;58(42):6235-6238. (PMID: 35510642) Chem Commun (Camb). 2015 Dec 4;51(93):16613-6. (PMID: 26447905) Cell. 1988 Feb 26;52(4):515-23. (PMID: 2963699) Anal Chem. 2011 May 1;83(9):3548-54. (PMID: 21449540) Nat Commun. 2019 Aug 7;10(1):3553. (PMID: 31391461) ACS Comb Sci. 2016 Jan 11;18(1):1-14. (PMID: 26652044) Signal Transduct Target Ther. 2025 Mar 05;10(1):74. (PMID: 40038239) Org Lett. 2021 Nov 05;23(21):8219-8223. (PMID: 34648297) J Med Chem. 2015 Dec 10;58(23):9354-70. (PMID: 26562070) Nat Commun. 2016 Mar 15;7:10914. (PMID: 26975182) Adv Sci (Weinh). 2024 Jul;11(28):e2400640. (PMID: 38810019) Oncoimmunology. 2017 May 12;6(7):e1328340. (PMID: 28811969) Small. 2024 Aug;20(33):e2401344. (PMID: 38708807) Angew Chem Int Ed Engl. 2026 Jul 27;65(31):e4556652. (PMID: 42272189) Molecules. 2013 Aug 16;18(8):9797-817. (PMID: 23959192) J Am Chem Soc. 2014 Nov 26;136(47):16563-73. (PMID: 25365776) J Pept Sci. 2009 Dec;15(12):799-807. (PMID: 19827002) Org Lett. 2019 May 3;21(9):3172-3177. (PMID: 31002255) Org Lett. 2024 Apr 12;26(14):2795-2799. (PMID: 37819674) Chemistry. 2025 Jun 17;31(34):e202501229. (PMID: 40322874) JACS Au. 2022 Nov 21;2(12):2821-2829. (PMID: 36590269) J Am Chem Soc. 2025 Mar 19;147(11):9576-9589. (PMID: 39885681) J Am Chem Soc. 2023 Feb 1;145(4):2305-2314. (PMID: 36657379) J Am Chem Soc. 2019 Mar 13;141(10):4167-4181. (PMID: 30768253) J Org Chem. 2023 Nov 3;88(21):15130-15141. (PMID: 37877589) Methods Enzymol. 1977;47:407-30. (PMID: 927196) Chembiochem. 2021 May 14;22(10):1779-1783. (PMID: 33493390) Angew Chem Int Ed Engl. 2014 Feb 10;53(7):1877-80. (PMID: 24474668) J Org Chem. 2014 Dec 19;79(24):11970-80. (PMID: 25222638) Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6799-6806. (PMID: 33350010) J Immunol. 2021 Jun 1;206(11):2566-2582. (PMID: 33911008) Org Lett. 2005 Feb 17;7(4):581-4. (PMID: 15704899) Angew Chem Int Ed Engl. 2023 Aug 21;62(34):e202307782. (PMID: 37389988) Angew Chem Int Ed Engl. 2025 Sep 8;64(37):e202509854. (PMID: 40734244) Anal Biochem. 1982 Jan 15;119(2):450-5. (PMID: 6280514) Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10766-10770. (PMID: 28685950) Angew Chem Int Ed Engl. 2019 Feb 25;58(9):2700-2704. (PMID: 30589179) Chemistry. 2019 Jun 21;25(35):8225-8228. (PMID: 30986322) Angew Chem Int Ed Engl. 2011 Feb 7;50(6):1232-40. (PMID: 21290490) |
| Grant Information: | Federal Ministry of Education and Research; Ministry of Science, Research and Arts Baden-Württemberg; Deutsche Forschungsgemeinschaft; Dieter Schwarz Foundation; Max Planck Society; HORIZON-HLTH-2024-DISEASE-08 European Union |
| Contributed Indexing: | Keywords: click chemistry; dengue protease inhibitors; late‐stage functionalization; peptide thioesters; peptides |
| Substance Nomenclature: | 0 (Peptides) 0 (Triazoles) 0 (Esters) 0 (Azides) 0 (Alkynes) 0 (Sulfhydryl Compounds) |
| Entry Date(s): | Date Created: 20260713 Date Completed: 20260914 Latest Revision: 20260916 |
| Update Code: | 20260916 |
| PubMed Central ID: | PMC13573147 |
| DOI: | 10.1002/anie.8315692 |
| PMID: | 42441694 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!