# Novel platforms for the discovery of bioactive small molecules

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2024 · $731,551

## Abstract

Project Summary
DNA-encoded library (DEL) technology has revolutionized the discovery of protein-
binding small molecules. We have developed a novel variant of this technology in which
the libraries are synthesized on tiny, hydrophilic beads using solid-phase synthesis
techniques and screened by incubation with fluorescently labeled, soluble proteins. This
platform will be employed to discover a plethora of new ligands for the proteasome and
other proteins involved in the Ubiquitin Proteasome System (UPS). They will serve as
probe molecules and drug leads for manipulating the UPS, which is critical for
maintaining protein homeostasis. An additional outcome of this work will be the
development of a new class of degraders that delivers a target protein directly to the
proteasome without the requirement for target Ubiquitylation. Finally, a nascent system
that allows screening DELs in cell-based assays will be optimized and utilized to discover
proteasome activators that can be used to test models of UPS dysfunction as a root cause
of aging and various degenerative diseases.

## Key facts

- **NIH application ID:** 10757142
- **Project number:** 1R35GM151875-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Thomas J. Kodadek
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $731,551
- **Award type:** 1
- **Project period:** 2024-02-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757142

## Citation

> US National Institutes of Health, RePORTER application 10757142, Novel platforms for the discovery of bioactive small molecules (1R35GM151875-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10757142. Licensed CC0.

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