Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide
Publication date
2022-10-01
Authors
Yang, Xin
Kemmink, Johan
Rijkers, Dirk T S
Liskamp, Rob M.J.
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Advisors
Supervisors
Document Type
Article
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Abstract
A ring-closing metathesis (RCM) - peptide coupling - ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) strategy was developed to synthesize a tricyclic hexapeptide in which the side chain to side chain connectivity pattern resulted in a mimic with a topology that effectively mimics the bioactivity of vancomycin as a potent binder of the bacterial cell wall D-Ala-D-Ala dipeptide sequence and more importantly being an effective inhibitor of bacterial growth.
Keywords
Macrocycles, Peptides, Peptidomimetics, Ring-closing metathesis, Ru-based azide alkyne cycloaddition, Biochemistry, Molecular Medicine, Molecular Biology, Pharmaceutical Science, Drug Discovery, Clinical Biochemistry, Organic Chemistry
Citation
Yang, X, Kemmink, J, Rijkers, D T S & Liskamp, R M J 2022, 'Synthesis of a tricyclic hexapeptide –via two consecutive ruthenium-catalyzed macrocyclization steps– with a constrained topology to mimic vancomycin's binding properties toward D-Ala-D-Ala dipeptide', Bioorganic & Medicinal Chemistry Letters, vol. 73, 128887. https://doi.org/10.1016/j.bmcl.2022.128887