# Syntheses of Bactobolin and Acybolin Antibiotics for Biological Studies of Analogues

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2021 · $209,821

## Abstract

PROJECT SUMMARY
 Since the commercialization of penicillin in 1928, antibiotics have been hailed as “magic bullets”. In recent
years, however, the number of bacterial strains resistant to clinically used antibiotics has sharply increased. The
lack of viable first-line treatments of these bacterial infections has forced clinicians to consider second-line
antibiotic options such as polymyxins and aminoglycosides, traditionally avoided because of significant toxicity.
Thus, the development of antibiotics with new mechanisms of action for the control of pernicious bacterial
infections is of vital importance. The synthesis of natural products and simplified derivatives has been a
particularly successful strategy for the enrichment of the anti-bacterial armamentarium. The specific aims of this
proposal are: 1. Completion of the first enantiospecific synthesis of Acybolin A and the second
enantiospecific synthesis of Bactobolins A-B. Bactobolins A-B are two broad spectrum natural product
antibiotics whose mechanism of action is the inhibition of protein translation via binding to an unprecedented site
of the 50S ribosomal subunit and displacing tRNA bound at the P site. Acybolin A is a recently isolated antibiotic
which shares strong structural homology to the Bactobolins but, excitingly, retains antibiotic activity against
Bactobolin-resistant strains of B. subtilis. The biological basis underlying such disparate activity remains
unknown. 2. Generation and evaluation of a plethora of functional analogues for future medicinal
chemistry efforts. The rationale for this proposed research is that its success would allow for access to a diverse
collection of antibacterial compounds with modes of action that are likely mechanistically distinct from FDA-
approved antibiotics. The expected outcome of this research is the completion of several important steps towards
the timely development of new, broad-spectrum, tolerable antibiotics and probe compounds for microbiological
studies. The successful execution of the research proposed herein is expected to have a significant positive
impact by aiding the global effort to reduce human morbidity and mortality resulting from pernicious bacterial
infections.

## Key facts

- **NIH application ID:** 10270504
- **Project number:** 2P20GM113117-06
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Shyam Sathyamoorthi
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,821
- **Award type:** 2
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270504

## Citation

> US National Institutes of Health, RePORTER application 10270504, Syntheses of Bactobolin and Acybolin Antibiotics for Biological Studies of Analogues (2P20GM113117-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10270504. Licensed CC0.

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