A conformationally constrained fused tricyclic nisin AB-ring system mimic toward an improved pyrophosphate binder of lipid II

作者：Harmsen Rianne A G; Ghalit Nourdin; Kemmink Johan; Breukink Eefjan; Liskamp Rob M J; Rijkers Dirk T S^*

来源：Tetrahedron, 2014, 70(42): 7691-7699.

DOI：10.1016/j.tet.2014.06.023

• Antibiotics
• Biomimetic synthesis
• Lantibiotics
• Molecular recognition
• Peptides and peptidomimetics
• Ring-closing metathesis

The bacteria-specific membrane component lipid Ills essential for bacterial cell wall synthesis. A tricyclic nisin mimic was designed and synthesized in which both thioether moieties were mimicked by an alkane-bridge, as well as the introduction of a third conformational constraint consisting of a macrocyclic lactam-bridge between the N-terminus and the B-ring. The newly designed tricyclic AB-ring mimic was found to bind lipid II since it was able to inhibit nisin-induced membrane leakage in a dose-dependent manner. These results imply that the tricyclic AB-ring mimic may form a novel class of lead structures for the development of nisin-based peptide antibiotics.

• 出版日期2014-10-21