Academic Journal
Light-Mediated Desulfurization of Peptides in Multi-Well Format for Combinatorial Library Synthesis.
| Τίτλος: | Light-Mediated Desulfurization of Peptides in Multi-Well Format for Combinatorial Library Synthesis. |
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| Συγγραφείς: | Jacobsen EA; Gubra, 2970 Hørsholm, Denmark.; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Lava J; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Thorseth A; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Corell DD; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Dam-Hansen C; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Gotfredsen CH; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark., Kræmer M; Gubra, 2970 Hørsholm, Denmark., Tran P; Gubra, 2970 Hørsholm, Denmark., Qvortrup K; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. |
| Πηγή: | Molecules (Basel, Switzerland) [Molecules] 2026 Sep 03; Vol. 31 (17). Date of Electronic Publication: 2026 Sep 03. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, c1995- |
| Ιατρικοί όροι (MeSH): | Peptides*/chemistry , Peptides*/chemical synthesis , Combinatorial Chemistry Techniques*/methods , Peptide Library* , Light*, Phosphines/chemistry ; Cysteine/chemistry ; Ultraviolet Rays |
| Περίληψη: | Native chemical ligation (NCL) combined with post-ligation desulfurization is a powerful strategy for the chemical joining of unprotected peptide segments to form larger polypeptides or to synthesize head-to-tail cyclized peptides. However, a simple, robust, and safe desulfurization protocol suitable for high-throughput synthesis workflows has yet to be developed. Here, we present a photochemical strategy in which desulfurization is achieved using 270 nm ultraviolet (UV) irradiation in the presence of tris(2-carboxyethyl)phosphine (TCEP). Optimization of reaction conditions resulted in reaction efficiency comparable with current chemical desulfurization methods. Desulfurization of a combinatorial peptide library confirmed that the photochemical desulfurization strategy is compatible with all canonical amino acids as well as thiol-protected cysteines. Implementation of the optimized conditions in a 96-well plate format using a custom-built light-emitting diode (LED) array confirmed that product formation is dependent on local light exposure. Increasing the distance between the plate and the light source enabled more uniform irradiation, giving homogenous product formation. Altogether, this study establishes UV-mediated desulfurization as a safe and scalable alternative for high-throughput peptide synthesis workflows. |
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| Grant Information: | NNF24OC0090589 Novo Nordisk Foundation |
| Contributed Indexing: | Keywords: cysteine desulfurization; high-throughput synthesis; macrocyclization; native chemical ligation; peptide synthesis; photochemistry |
| Substance Nomenclature: | 0 (Peptides) 0 (Peptide Library) 0 (Phosphines) K848JZ4886 (Cysteine) 22OAC2MO2S (tris(2-carboxyethyl)phosphine) |
| Entry Date(s): | Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260916 |
| Update Code: | 20260916 |
| PubMed Central ID: | PMC13566937 |
| DOI: | 10.3390/molecules31173097 |
| PMID: | 42738756 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1420-3049 |
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| DOI: | 10.3390/molecules31173097 |