# Harnessing Small Molecules to Probe the Structure and Function of Long Noncoding RNAs

> **NIH NIH R35** · DUKE UNIVERSITY · 2020 · $30,000

## Abstract

Harnessing Small Molecules to Probe the Structure and Function of Long
 Noncoding RNAs: Equipment Supplement
ABSTRACT
The long-term goal of the PI is to develop highly specific, RNA-targeted, small molecule ligands to probe the
dynamic structure, fundamental biology, and therapeutic potential of long noncoding RNAs (lncRNAs). Despite
the proposed therapeutic potential of lncRNAs, adequate small molecule targeting strategies have yet to be
realized. This slow progress is due in part to a gap in knowledge with respect to guiding principles and
methods for small molecule:RNA interactions. Our central hypothesis is that the parallel discovery of small
molecule chemical space and RNA topological space privileged for differentiation will yield fundamental
insights into small molecule:RNA recognition that can be applied to the rapid development of ligands with high
affinity and specificity for a wide range of RNA targets. In the proposed work, we simultaneously pursue two
independent but complementary lines of fundamental investigation and apply the developed guiding principles
and technologies to two critical lncRNA targets. In Area 1, we use cheminformatic analysis, organic synthesis,
and rapid screening methods to identify small molecule properties biased toward specific RNA recognition. In
Area 2, we use pattern recognition protocols to identify RNA structures that are readily differentiated by small
molecules. In Area 3, we combine our RNA-biased libraries and optimized screening assays to identify the first
inhibitors of lncRNA tertiary structure, particularly the 3’-triple helix of MALAT1. In Area 4, we use a wide range
of computational and experimental tools to identify small molecules that inhibit lncRNA:protein interactions, viz.
HOTAIR and its protein binding partner, PRC2. The rationale for this research is that our novel RNA-specific
libraries and technologies will enable new investigations of RNA structure and function and serve as a rich
platform for future development of RNA targeted therapeutics.
We are requesting an automated liquid dispenser, specifically the Multidrop Combi nL Reagent Dispenser
(Thermo Scientific), which will exponentially increase our ability to generate the necessary data to achieve
these goals.

## Key facts

- **NIH application ID:** 10135577
- **Project number:** 3R35GM124785-03S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Amanda E Hargrove
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,000
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135577

## Citation

> US National Institutes of Health, RePORTER application 10135577, Harnessing Small Molecules to Probe the Structure and Function of Long Noncoding RNAs (3R35GM124785-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135577. Licensed CC0.

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