NEW PERSPECTIVES ON MACROCYCLES FOR DRUG DISCOVERY
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Tethered Macrocyclic Peptides, a Novel Antibiotic Class Targeting Acinetobacter baumannii

Abstract: In the light of the rapidly rising number of people dying from bacterial infections and the lack of effective antibiotics, the Tethered Macrocyclic Peptide (MCP) Acinetobacter baumannii project addresses the urgent need to fight multi-drug resistant bacteria. The Tethered Macrocyclic Peptides represent a structurally distinct compound class selectively targeting Acinetobacter baumannii. The lecture will present the discovery and optimization of this compound class culminating in potent molecules that in vitro overcome pre-existing antibiotic resistance mechanisms and show in vivo efficacy in murine models of infection.

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Carsten Kroll
Roche Innovation Center, 
Basel, Switzerland
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Related publications:
Strategies for the Diversity-Oriented Synthesis of Macrocycles, K. T. Mortensen, T. J. Osberger, T. A. King, H. F. Sore, D. R. Spring, Chem. Rev. 2019, 119, 10288-10317.
A Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles, F. Nie, D. L. Kunciw, D. Wilcke, J. E. Stokes, W. R. J. D. Galloway, S. Bartlett, H. F. Sore, D. R. Spring, Angew. Chem. Int. Ed. 2016, 55, 11139-11143.
A New Strategy for the Diversity-Oriented Synthesis of Macrocyclic Scaffolds using Multi-Dimensional Coupling, H. S. G. Beckmann, F. Nie, C. E. Hagerman, H. Johansson, Y. S. Tan, D. Wilcke, D. R. Spring, Nature Chem. 2013, 5, 861-867.
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