# Tracking Glycosylation State with Fluorinated Glycosides Probes

> **NIH NIH P20** · UNIVERSITY OF MISSISSIPPI · 2020 · $247,634

## Abstract

Project Summary
 Glycosylated natural products are widespread in nature and have secured a prominent role in the
treatment of many diseases in humans. The antibiotics, vancomycin and erythromycin, and the anticancer
agents, doxorubicin and bleomycin, are remarkable examples. Additionally, some pharmaceuticals have been
designed from glycosylated natural products, and a recent instance is the development of the natural product,
phlorizin, into the sodium-glucose co-transporter-2 (SGLT2) class of antidiabetic drugs in which canagliflozin
(Invokana®) was the first-in-class. In this case, phlorizin displays glucose which is crucial for its interaction at the
SGLT2 transporter; however, the glycoside linkage is unstable and rapidly de-glycosylated. Thus, the design of
derivatives of phlorizin that were resistant to de-glycosylation was instrumental in its translation to canagliflozin.
Recently, glycosylated polyphenolic natural products called anthocyanins have demonstrated substantial
potential in age-related neurodegeneration and diseases such as Parkinson's and Alzheimer's disease.
Unfortunately, clinical studies have shown that the sugar moieties of the glycosylated anthocyanins are rapidly
hydrolyzed during digestion to give the anthocyanin aglycones, and the respective aglycones are poorly soluble,
unstable, and generally devoid of biological effects. This metabolic liability of the anthocyanins has blocked their
translational potential. However, there is a critical biomedical need to discover new treatment strategies in all
three of these conditions. In this project, we will design derivatives of anthocyanins, where the sugar group
cannot be hydrolyzed. In our in vivo studies, we have already validated the presence of a natural anthocyanin in
the pooled serum of rats following oral dosing but its absence in homogenized liver samples. We have recently
developed a new synthetic method to replace an unstable glycosyl linkage with a stable, fluorinated methyl
group. Additionally, these fluorinated groups will serve as probes for tracking glycosylation state by F-NMR. Our
goal is to design and track metabolically stable glycosylated anthocyanins and demonstrate enhanced stability
in vitro and in rodents. This project has the potential to deliver a substantial impact, because a method to add
fluorinated sugars to organic molecules is an unaddressed challenge. Also, tracking an enhancement in the
metabolic stability of fluorinated derivatives of the anthocyanins will contribute to advancing the translational
potential of these glycosylated natural products.

## Key facts

- **NIH application ID:** 9853998
- **Project number:** 1P20GM130460-01A1
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI
- **Principal Investigator:** David A Colby
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,634
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853998

## Citation

> US National Institutes of Health, RePORTER application 9853998, Tracking Glycosylation State with Fluorinated Glycosides Probes (1P20GM130460-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853998. Licensed CC0.

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