Grants and Contracts Details
Description
In this proposed study, we will utilize the information obtained from the solved structure of the bacterial
ribosome and recent year's progress in the understanding of how ribosome-targeting antibiotics bind to their
ribosomal target site for the development of novel families of antimicrobial agents. In designing the proposed
novel ribosome-targeting antibiotics, we will focus on strategies to evade several bacterial resistance
mechanisms and offer new directions for structure-based development of broad-spectrum antibiotics. The
design of the novel antimicrobial agents will be based on the incorporation of binding motifs from P-site and Asite
targeting antibiotics to form novel molecules that will interact with the bacterial ribosome using novel sets
of interactions. We will study the protein synthesis inhibition potency of the novel antimicrobials by in vitro and
in vivo translation assays. We will also study the ability of the proposed antimicrobials to evade the action of a
large variety of antibiotic-deactivating enzymes, which are currently one of the leading causes for the loss of
efficacy of clinically used ribosome-targeting antibiotics. The antimicrobial activities of the novel antibiotics will
be studied by several microbiological tests on a broad spectrum of pathogenic and drug-resistant Grampositive
and Gram-negative bacterial strains. To achieve our proposed research goals, we will integrate the
organic chemistry and microbiological expertise of the Fridman group with the biochemical, microbiological,
and crystallography expertise of the Garneau-Tsodikova group. The results of the proposed research are likely
lead to novel antibiotics with unique target binding modes and efficacy against a variety of bacteria.
Status | Finished |
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Effective start/end date | 10/1/13 → 9/30/17 |
Funding
- US-Israel Binational Science Foundation: $115,770.00
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