# Protein Chemistry

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $408,438

## Abstract

PROJECT SUMMARY/ABSTRACT
The human body contains two million or so distinct proteins. Chemistry harbors
the potential to endow these proteins with attributes desirable for biomedicine.
The proposed research takes advantage of new chemical reactivity that is
applicable in a physiological context. The overall goal is to develop a facile,
general means to endow native proteins with the ability to enter the cytosol of
human cells. The strategy is to O-alkylate protein carboxyl groups by using a
tuned diazo compound, generating esters that are analogous to those in small-
molecule prodrugs. Intracellular esterases make these modifications traceless,
avoiding any compromise to proper function or potential for immunogenicity.
“Protein esterification” has an uncharted landscape. Accordingly, work will begin
by exploring fundamental attributes of esterified proteins, including the
mechanism of cellular uptake and the enzymology of ester hydrolysis by cellular
esterases in vitro and in cellulo (Aim 1). Esterification will then be used to deliver
proteins for tumor suppression (Aim 2), genome editing (Aim 3), and anti-viral
activity (Aim 4). The work relies on methods and ideas from organic chemistry,
enzymology, chemical biology, and related fields, and is designed to establish a
new paradigm for developing chemotherapeutic agents that are capable of
addressing numerous unmet medical needs.

## Key facts

- **NIH application ID:** 10226825
- **Project number:** 5R01GM044783-29
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ronald T Raines
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,438
- **Award type:** 5
- **Project period:** 1990-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226825

## Citation

> US National Institutes of Health, RePORTER application 10226825, Protein Chemistry (5R01GM044783-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10226825. Licensed CC0.

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