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Light-Mediated Desulfurization of Peptides in Multi-Well Format for Combinatorial Library Synthesis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Light-Mediated Desulfurization of Peptides in Multi-Well Format for Combinatorial Library Synthesis.
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.
References: Chembiochem. 2012 Mar 5;13(4):542-6. (PMID: 22302623)
J Am Chem Soc. 2023 Jan 18;145(2):1053-1061. (PMID: 36602440)
Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14607-14611. (PMID: 28971554)
Signal Transduct Target Ther. 2022 Feb 14;7(1):48. (PMID: 35165272)
Org Lett. 2016 Mar 4;18(5):1166-9. (PMID: 26892036)
Angew Chem Int Ed Engl. 2007;46(48):9248-52. (PMID: 18046687)
Mol Imaging Biol. 2010 Aug;12(4):377-85. (PMID: 19937135)
Org Lett. 2012 Mar 16;14(6):1520-3. (PMID: 22360701)
Angew Chem Int Ed Engl. 2008;47(36):6807-10. (PMID: 18626881)
Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11634-11639. (PMID: 29908104)
Chembiochem. 2010 Jun 14;11(9):1232-5. (PMID: 20437446)
Front Microbiol. 2020 Feb 21;11:168. (PMID: 32153522)
Org Lett. 2025 Feb 7;27(5):1159-1163. (PMID: 39848618)
Biochim Biophys Acta. 1998 Sep 8;1387(1-2):195-205. (PMID: 9748574)
Int J Mol Sci. 2025 May 27;26(11):. (PMID: 40507941)
J Pept Sci. 2005 Oct;11(10):642-9. (PMID: 15864815)
Protein J. 2004 May;23(4):287-94. (PMID: 15214499)
J Pept Sci. 2007 May;13(5):348-53. (PMID: 17436344)
Org Biomol Chem. 2017 Mar 28;15(12):2491-2496. (PMID: 28170021)
Signal Transduct Target Ther. 2025 Mar 05;10(1):74. (PMID: 40038239)
J Neurosci. 1993 Apr;13(4):1676-87. (PMID: 8463843)
J Am Chem Soc. 2018 Jul 25;140(29):9020-9024. (PMID: 29792427)
Org Biomol Chem. 2022 Sep 21;20(36):7343-7350. (PMID: 36073340)
J Am Chem Soc. 2015 Jun 10;137(22):7197-209. (PMID: 25978693)
J Am Chem Soc. 2025 Feb 05;147(5):4135-4146. (PMID: 39849831)
Angew Chem Int Ed Engl. 2013 Sep 9;52(37):9723-7. (PMID: 23893778)
Arch Biochem Biophys. 2007 Jun 1;462(1):94-102. (PMID: 17466930)
Science. 1994 Nov 4;266(5186):776-9. (PMID: 7973629)
Chem Soc Rev. 2021 Jan 7;50(1):39-57. (PMID: 33174541)
Org Lett. 2014 Jan 3;16(1):290-3. (PMID: 24294973)
Org Lett. 2024 Apr 5;26(13):2590-2595. (PMID: 38517348)
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
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  Data: Light-Mediated Desulfurization of Peptides in Multi-Well Format for Combinatorial Library Synthesis.
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  Data: <searchLink fieldCode="AU" term="%22Jacobsen+EA%22">Jacobsen EA</searchLink>; Gubra, 2970 Hørsholm, Denmark.; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Lava+J%22">Lava J</searchLink>; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Thorseth+A%22">Thorseth A</searchLink>; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Corell+DD%22">Corell DD</searchLink>; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Dam-Hansen+C%22">Dam-Hansen C</searchLink>; Department of Electrical and Photonics Engineering, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Gotfredsen+CH%22">Gotfredsen CH</searchLink>; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Kræmer+M%22">Kræmer M</searchLink>; Gubra, 2970 Hørsholm, Denmark.<br /><searchLink fieldCode="AU" term="%22Tran+P%22">Tran P</searchLink>; Gubra, 2970 Hørsholm, Denmark.<br /><searchLink fieldCode="AU" term="%22Qvortrup+K%22">Qvortrup K</searchLink>; Department of Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
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  Data: <searchLink fieldCode="JN" term="%22100964009%22">Molecules (Basel, Switzerland)</searchLink> [Molecules] 2026 Sep 03; Vol. 31 (17). <i>Date of Electronic Publication: </i>2026 Sep 03.
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  Data: <searchLink fieldCode="MM" term="%22Peptides%22">Peptides*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptides%22">Peptides*</searchLink>/<searchLink fieldCode="MM" term="%22Peptides+chemical+synthesis%22">chemical synthesis</searchLink> <br /><searchLink fieldCode="MM" term="%22Combinatorial+Chemistry+Techniques%22">Combinatorial Chemistry Techniques*</searchLink>/<searchLink fieldCode="MM" term="%22Combinatorial+Chemistry+Techniques+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Peptide+Library%22">Peptide Library*</searchLink> <br /><searchLink fieldCode="MM" term="%22Light%22">Light*</searchLink><br /><searchLink fieldCode="MH" term="%22Phosphines%22">Phosphines</searchLink>/<searchLink fieldCode="MH" term="%22Phosphines+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Cysteine%22">Cysteine</searchLink>/<searchLink fieldCode="MH" term="%22Cysteine+chemistry%22">chemistry</searchLink> ; <searchLink fieldCode="MH" term="%22Ultraviolet+Rays%22">Ultraviolet Rays</searchLink>
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  Label: Abstract
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  Data: 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.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Chembiochem. 2012 Mar 5;13(4):542-6. (PMID: <searchLink fieldCode="PM" term="%2222302623%22">22302623)</searchLink><br />J Am Chem Soc. 2023 Jan 18;145(2):1053-1061. (PMID: <searchLink fieldCode="PM" term="%2236602440%22">36602440)</searchLink><br />Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14607-14611. (PMID: <searchLink fieldCode="PM" term="%2228971554%22">28971554)</searchLink><br />Signal Transduct Target Ther. 2022 Feb 14;7(1):48. (PMID: <searchLink fieldCode="PM" term="%2235165272%22">35165272)</searchLink><br />Org Lett. 2016 Mar 4;18(5):1166-9. (PMID: <searchLink fieldCode="PM" term="%2226892036%22">26892036)</searchLink><br />Angew Chem Int Ed Engl. 2007;46(48):9248-52. (PMID: <searchLink fieldCode="PM" term="%2218046687%22">18046687)</searchLink><br />Mol Imaging Biol. 2010 Aug;12(4):377-85. (PMID: <searchLink fieldCode="PM" term="%2219937135%22">19937135)</searchLink><br />Org Lett. 2012 Mar 16;14(6):1520-3. (PMID: <searchLink fieldCode="PM" term="%2222360701%22">22360701)</searchLink><br />Angew Chem Int Ed Engl. 2008;47(36):6807-10. (PMID: <searchLink fieldCode="PM" term="%2218626881%22">18626881)</searchLink><br />Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11634-11639. (PMID: <searchLink fieldCode="PM" term="%2229908104%22">29908104)</searchLink><br />Chembiochem. 2010 Jun 14;11(9):1232-5. (PMID: <searchLink fieldCode="PM" term="%2220437446%22">20437446)</searchLink><br />Front Microbiol. 2020 Feb 21;11:168. (PMID: <searchLink fieldCode="PM" term="%2232153522%22">32153522)</searchLink><br />Org Lett. 2025 Feb 7;27(5):1159-1163. (PMID: <searchLink fieldCode="PM" term="%2239848618%22">39848618)</searchLink><br />Biochim Biophys Acta. 1998 Sep 8;1387(1-2):195-205. (PMID: <searchLink fieldCode="PM" term="%229748574%22">9748574)</searchLink><br />Int J Mol Sci. 2025 May 27;26(11):. (PMID: <searchLink fieldCode="PM" term="%2240507941%22">40507941)</searchLink><br />J Pept Sci. 2005 Oct;11(10):642-9. (PMID: <searchLink fieldCode="PM" term="%2215864815%22">15864815)</searchLink><br />Protein J. 2004 May;23(4):287-94. (PMID: <searchLink fieldCode="PM" term="%2215214499%22">15214499)</searchLink><br />J Pept Sci. 2007 May;13(5):348-53. (PMID: <searchLink fieldCode="PM" term="%2217436344%22">17436344)</searchLink><br />Org Biomol Chem. 2017 Mar 28;15(12):2491-2496. (PMID: <searchLink fieldCode="PM" term="%2228170021%22">28170021)</searchLink><br />Signal Transduct Target Ther. 2025 Mar 05;10(1):74. (PMID: <searchLink fieldCode="PM" term="%2240038239%22">40038239)</searchLink><br />J Neurosci. 1993 Apr;13(4):1676-87. (PMID: <searchLink fieldCode="PM" term="%228463843%22">8463843)</searchLink><br />J Am Chem Soc. 2018 Jul 25;140(29):9020-9024. (PMID: <searchLink fieldCode="PM" term="%2229792427%22">29792427)</searchLink><br />Org Biomol Chem. 2022 Sep 21;20(36):7343-7350. (PMID: <searchLink fieldCode="PM" term="%2236073340%22">36073340)</searchLink><br />J Am Chem Soc. 2015 Jun 10;137(22):7197-209. (PMID: <searchLink fieldCode="PM" term="%2225978693%22">25978693)</searchLink><br />J Am Chem Soc. 2025 Feb 05;147(5):4135-4146. (PMID: <searchLink fieldCode="PM" term="%2239849831%22">39849831)</searchLink><br />Angew Chem Int Ed Engl. 2013 Sep 9;52(37):9723-7. (PMID: <searchLink fieldCode="PM" term="%2223893778%22">23893778)</searchLink><br />Arch Biochem Biophys. 2007 Jun 1;462(1):94-102. (PMID: <searchLink fieldCode="PM" term="%2217466930%22">17466930)</searchLink><br />Science. 1994 Nov 4;266(5186):776-9. (PMID: <searchLink fieldCode="PM" term="%227973629%22">7973629)</searchLink><br />Chem Soc Rev. 2021 Jan 7;50(1):39-57. (PMID: <searchLink fieldCode="PM" term="%2233174541%22">33174541)</searchLink><br />Org Lett. 2014 Jan 3;16(1):290-3. (PMID: <searchLink fieldCode="PM" term="%2224294973%22">24294973)</searchLink><br />Org Lett. 2024 Apr 5;26(13):2590-2595. (PMID: <searchLink fieldCode="PM" term="%2238517348%22">38517348)</searchLink>
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  Data: <i>Keywords: </i>cysteine desulfurization; high-throughput synthesis; macrocyclization; native chemical ligation; peptide synthesis; photochemistry
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      – SubjectFull: Cysteine chemistry
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      – SubjectFull: Ultraviolet Rays
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