Academic Journal
Genetically Encoded Lysine-Selective Photocyclization Enables Phage Display Selection of Cyclic Peptide Binders.
| Τίτλος: | Genetically Encoded Lysine-Selective Photocyclization Enables Phage Display Selection of Cyclic Peptide Binders. |
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| Συγγραφείς: | Yang XQ; State Key Laboratory of Natural Product Chemistry, Lanzhou Magnetic Resonance Center, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China., Ming W; State Key Laboratory of Natural Product Chemistry, Lanzhou Magnetic Resonance Center, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China.; State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai, P. R. China., Zhang ZH; State Key Laboratory of Natural Product Chemistry, Lanzhou Magnetic Resonance Center, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China., Liu X; State Key Laboratory of Natural Product Chemistry, Lanzhou Magnetic Resonance Center, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China., Bai LW; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, P. R. China., Li ZH; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, P. R. China., Huang R; School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, P. R. China., Chen XH; State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai, P. R. China.; School of Pharmaceutical Science and Technology, Hangzhou Institute For Advanced Study, University of Chinese Academy of Sciences, Hangzhou, P. R. China., Lei X; State Key Laboratory of Natural Product Chemistry, Lanzhou Magnetic Resonance Center, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, P. R. China. |
| Πηγή: | Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2026 Aug 24; Vol. 65 (35), pp. e3703404. Date of Electronic Publication: 2026 Jul 09. |
| 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, Cyclic*/chemistry , Peptides, Cyclic*/genetics , Peptides, Cyclic*/metabolism , Lysine*/chemistry , Lysine*/genetics , Peptide Library*, Cyclization ; Photochemical Processes |
| Περίληψη: | Genetically encoded macrocyclization strategies have expanded the cyclic peptide chemical space accessible to phage display but remain constrained by reliance on cysteine-based reactivity or hydrolytically unstable lysine-targeted reagents. Here, we introduce a lysine-selective and proximity-induced photocyclization platform enabled by the noncanonical amino acid o-nitrobenzyl alcohol lysine (o-NBAK), incorporated into phage-displayed peptides and activated using the mild and fully biocompatible PANAC photoclick reaction. Photocyclization proceeded efficiently on both purified pIII fusion proteins and intact phage particles with no detectable loss of infectivity, driven by intramolecular proximity between o-NBAK and a neighboring lysine, yielding well-defined stable indazolone macrocycles. Screening PANAC-cyclized libraries against disease-relevant proteins produced cyclic ligands with nanomolar to low-micromolar affinities, and cyclization enhanced proteolytic stability by more than an order of magnitude. These findings establish the first lysine-selective cyclic peptide library constructed on phage through ncAA incorporation and demonstrate a robust, chemoselective, and broadly applicable strategy for discovering bioactive cyclic peptides. (© 2026 Wiley‐VCH GmbH.) |
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| Grant Information: | 22ZD6FA006 the Science and Technology Major Program of Gansu Province of China; 23ZDFA015 the Science and Technology Major Program of Gansu Province of China; 2025CXZX-055 the Funds for Gansu Province Postgraduate Innovation Star Program |
| Contributed Indexing: | Keywords: PANAC reaction; macrocyclic peptides; noncanonical amino acids; phage display; photocyclization |
| Substance Nomenclature: | 0 (Peptides, Cyclic) K3Z4F929H6 (Lysine) 0 (Peptide Library) |
| Entry Date(s): | Date Created: 20260709 Date Completed: 20260824 Latest Revision: 20260916 |
| Update Code: | 20260916 |
| PubMed Central ID: | PMC13502564 |
| DOI: | 10.1002/anie.3703404 |
| PMID: | 42423217 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1521-3773 |
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| DOI: | 10.1002/anie.3703404 |