# Development of Small Molecule Probes for the Selective Modification and Labeling of the Mycobacterial Cell Wall

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $19,251

## Abstract

PROJECT SUMMARY/ABSTRACT
 All cells throughout the three domains of life are coated in an array of structurally and compositionally
diverse glycans which play a key role in cell signaling and recognition. In eukaryotic systems, a number of
strategies for the perturbation of these structures with unnatural sugar probes have been disclosed. These
probes have proven to be a powerful tool for interrogating glycan structure, function and dynamics in living
systems. However, because these techniques all rely on extensive metabolic processing of the probe prior to
incorporation, they have been largely ineffective in bacteria, which utilize a multitude of catabolic pathways that
can degrade and reconstitute parts of the probe on the way to the final destination. This proposal aims to
circumvent this problem by designing small molecule probes that engage directly with the extracellular enzymes
that construct important cell wall motifs. This strategy, termed ‘biosynthetic incorporation’ will be applied to the
selective modification of two important glycolipid virulence factors within the cell wall of Mycobacterium
tuberculosis (Mtb), the lipoarabinomannan (LAM) and trehalose dimycolate (TDM), which help the pathogen
infect host cells and evade the body’s immune defense system. This proposal focuses primarily on the design
and synthesis of azide-modified arabinofuranose, mannose and mycolic acid probes and studies intended to
quantify the degree of incorporation and distribution of the probes. The tools developed in the course of this work
will be used to visualize the localization and dynamics of the LAM and TDM during host cell infection using live
cell imaging. Insights gleaned from these studies could elucidate new strategies for the treatment of
mycobacterial diseases like Mtb.
 The Kiessling research group at the Massachusetts Institute of Technology (MIT) is an ideal environment
to pursue the research outlined in this proposal and to achieve the training goals that will prepare me for a career
in academia. In the Kiessling group, I will be able to continue to hone and utilize my skills in synthetic organic
chemistry while also gaining expertise in a diverse array of new techniques including microscopy, microbiology,
flow cytometry and cell culture. I will have the opportunity to mentor undergraduates and graduate students
within the group. In addition to this, the MIT Teaching and Learning Lab provides programming and a number of
resources that I will utilize in order to continue to build my teaching skills. I am confident that the exceptional
laboratory and institutional environment at MIT will provide me with the tools necessary for a successful
independant career.

## Key facts

- **NIH application ID:** 10394129
- **Project number:** 5F32GM142288-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Daria Eldarovna Kim
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $19,251
- **Award type:** 5
- **Project period:** 2021-04-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394129

## Citation

> US National Institutes of Health, RePORTER application 10394129, Development of Small Molecule Probes for the Selective Modification and Labeling of the Mycobacterial Cell Wall (5F32GM142288-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10394129. Licensed CC0.

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