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Synthesis and rational design of next-generation ribosome-targeting inhibitors


EMSL Project ID
51279

Abstract

Antibiotic resistance is an urgent threat to public health. CryoEM of the bacterial ribosome affords insight into the interactions between organic inhibitor scaffolds, the RNA, and even the nascent peptide chain, enabling structure guided design. First, we will examine the streptogramin class, with new capabilities to modify the streptogramin scaffold (by the Seiple lab at UCSF), we aim to use CryoEM to guide the development of new analogues that counter resistance. Second, we will examine oxazolidinones to determine how select inhibitors (including novel analogues synthesized by the Fujimori lab at UCSF) are active against Cfr-modified ribosomes. We have routinely been able to obtain high resolution data; however, we have limited access to the Titan Krios microscopes at UCSF. These shared instruments are oversubscribed due to the heavy usage of four core user groups, leaving non-core users to seek access through mechanisms such as this.

Project Details

Start Date
2020-02-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

James Fraser
Institution
University of California, San Francisco

Team Members

David Lee
Institution
University of California, San Francisco

Jenna Pellegrino
Institution
University of California, San Francisco

Theo Humphreys
Institution
Oregon Health & Science University