# Molecular Cloaking Devices for Manipulation of Cysteine Post-Translational Modifications

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $496,766

## Abstract

Project Summary
Post-translational modifications (PTMs) of proteins are involved in virtually all cellular signaling pathways.
Pharmacological intervention in these events is an important strategy for drug development. In this project, we
propose to establish a novel platform for the discovery of covalent inhibitors of cysteine post-translational
modifications, in particular, the prenylation of the C-termini of H-Ras and K-Ras. These events are critical for
oncogenic mutants of these proteins to drive cell uncontrolled growth and division. In contrast to typical
strategies for blocking PTMs, we will screen for non-peptidic macrocycles that bind covalently to the modified
epitope on the substrate protein (H-Ras or K-Ras), rather than compounds that target the modifying enzyme. In
this way, we believe it will be possible to manipulate single PTMs with unprecedented selectivity.

## Key facts

- **NIH application ID:** 10507541
- **Project number:** 1R21CA273954-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Thomas J. Kodadek
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $496,766
- **Award type:** 1
- **Project period:** 2022-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507541

## Citation

> US National Institutes of Health, RePORTER application 10507541, Molecular Cloaking Devices for Manipulation of Cysteine Post-Translational Modifications (1R21CA273954-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10507541. Licensed CC0.

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