Peptide stapling by late-stage Suzuki-Miyaura cross-coupling
| Autor: | Gruss, Hendrik, Feiner, Rebecca C., Mseya, Ridhiwan, Schroeder, David C., Jewginski, Michat, Mueller, Kristian M., Latajka, Rafat, Marıon, Antoıne, Sewald, Norbert |
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| Přispěvatelé: | OpenMETU |
| Rok vydání: | 2022 |
| Předmět: |
halotryptophan
ARYLATION STABILITY macrocyclisation stapled peptides MILD molecular dynamics SIMULATIONS late-stage diversification TRYPTOPHAN intrinsically disordered peptides ALPHA-HELICAL PEPTIDES accelerated molecular dynamics ACCELERATED MOLECULAR-DYNAMICS DIVERSIFICATION ENZYMATIC HALOGENATION Suzuki-Miyaura cross-coupling MACROCYCLIZATION |
| Popis: | The development of peptide stapling techniques to stabilise alpha-helical secondary structure motifs of peptides led to the design of modulators of protein-protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki-Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased alpha-helicity and enhanced binding affinity to its native binding partner beta-catenin. An increased proteolytic stability against proteinase K has been demonstrated. |
| Databáze: | OpenAIRE |
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