# Supplement to Chemical Biology Studies of the Dynamics and Inhibition of Peptidoglycan Biosynthesis

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $138,930

## Abstract

Funding Opportunity Announcement (FOA) Number: PA-20-272
Equipment request for Maximizing Investigators' Research Award R35 136365 (Project Title: Chemical
Biology Studies of the Dynamics and Inhibition of Peptidoglycan Biosynthesis)
PROJECT SUMMARY
 This equipment request is being made to significantly enhance our research capabilities in
support of our R35 MIRA award. Our funded MIRA application represents the fusion of two
complementary research programs that are, broadly described, directed at the urgent public health
threat posed by antibiotic resistance. Our MIRA award seeks to capitalize on our discovery of
fluorescent D-amino acids (FDAAs) that have provided unprecedented, and heretofore unavailable,
tools for the visualization of bacterial cell wall peptidoglycan (PG) dynamics in real time and in live
bacterial cells. We have initiated additional studies to elucidate the details of bacterial cell division and
cell separation in Bacillus subtilis, and we are seeking to develop new classes of fluorogenic (i.e., “turn-
on”) probes that will enable the study of PG synthesis and dynamics in real-time and in live bacterial
cells. We will also continue our effort directed at the synthesis and mechanistic study of cyclic
depsipeptide antibiotics that inhibit PG biosynthesis. Furthermore, we have recently uncovered data
that suggest the cyclic depsipeptides may have a second mechanism of action that involves inhibition
of lipid recycling, an essential activity in the PG biosynthesis pathway. The lipid recycling pathway
remains to be clearly elucidated and, when coupled with dual-mode activity that may be inherent to
these cyclic depsipeptides under study, very promising new avenues for the identification of new
antibacterial targets and development of new antibacterial agents are likely to emerge from this
research effort.
 Research in each of these areas requires routine access to HPLC instrumentation with high
resolution capabilities with multiple mods of detection. Our current HPLC system is approximately
twenty years old and is no longer supported by the manufacturer. In addition, the computer system
required to run the instrument has become obsolete and is no longer supported by our university. As a
result, this instrument has a significant amount of ‘down time’ that adversely impacts research progress
under the parent R35 award. In this application, we are seeking funds for the purchase of an Agilent
1290 Infinity Flex Series HPLC/UHPLC instrument that has the capability for routine purity analysis of
amino acids, cyclic peptides, and the like as well as UHPLC capability to enable analysis of more
complex samples, such as PG fragments. This instrument will replace our aging and unrepairable
system, significantly enhance our analytical capabilities, and have a profoundly positive impact on our
activities under the parent R35 award.

## Key facts

- **NIH application ID:** 10609340
- **Project number:** 3R35GM136365-03S1
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Michael S VanNieuwenhze
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $138,930
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609340

## Citation

> US National Institutes of Health, RePORTER application 10609340, Supplement to Chemical Biology Studies of the Dynamics and Inhibition of Peptidoglycan Biosynthesis (3R35GM136365-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10609340. Licensed CC0.

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