# Esterase Specificity for Pharmacology and Chemical Biology

> **NIH NIH R21** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $249,180

## Abstract

PROJECT SUMMARY/ABSTRACT
Few molecules in human cells contain esters. Likewise, human cells have high
esterase activity. That activity is exploited routinely for the delivery of
pharmacological agents as prodrugs in which carboxyl moieties are masked as
esters. The esters in prodrugs are typically made with ethanol, which is not toxic
as a byproduct of ester hydrolysis. Although esterases vary in different tissues
and cell types, variations in esterase specificity are not exploited in the current
pharmacopeia. The proposed research seeks to provide the technological basis for
tailoring the alcohol portion of prodrugs (and latent probes) to particular
physiological contexts. Work will begin by developing a high-throughput assay
for the esterase-catalyzed hydrolysis of alkyl esters in which the alcohol protein of
the ester is a variable. Then, a library of esters will be synthesized by reacting
alcohols with a common intermediate. Finally, a profile of esterase substrate
specificity will be developed across a wide range of tissues, cell types, and sera.
The ensuing profile of the substrate specificity of esterases endogenous in
contexts most relevant for both drug development and basic research in chemical
biology will enable future efforts to take prodrug and latent probe design into a
new realm.

## Key facts

- **NIH application ID:** 10017292
- **Project number:** 5R21GM135780-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ronald T Raines
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,180
- **Award type:** 5
- **Project period:** 2019-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017292

## Citation

> US National Institutes of Health, RePORTER application 10017292, Esterase Specificity for Pharmacology and Chemical Biology (5R21GM135780-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10017292. Licensed CC0.

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