# Enhanced Raman Imaging of Ligand-Receptor Recognition

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $346,407

## Abstract

Enhanced Raman Imaging of Ligand-Receptor Recognition
Abstract:
 The goal of this proposal is to identify molecular interactions relevant to drug targeting and chemical
signaling in living cells. A critical bottleneck in the development of drugs is the identification of off-target effects.
Methods that can identify the molecular interactions associated with proteins recognizing and binding to drug
candidates in cellular and other live models can be used to understand and minimize unwanted side effects
and complications. Identifying these effects at earlier stages of drug screening is important to avoid late stage
drug failure. We are developing technologies that take advantage of the plasmonic properties of metallic
nanoparticles to enable chemical-specific spectroscopic studies of ligand-receptor binding in living cells. These
investigations will provide new approaches to probing the receptor’s chemical residues that bind peptide
antagonists and provide insights into molecular interactions that regulate the proteins involved in signaling and
drug targeting.
 Our approach combines enhanced Raman scattering from both nanoparticles (Surface enhanced Raman
scattering, or SERS) and scanning probes (tip enhanced Raman scattering, or TERS), nanoparticle tracking
microscopy, non-standard applications of static and dynamic quantum chemical calculations, and super-
resolution SERS imaging to characterize chemical interactions that regulate binding to protein receptors.
Information present in the enhanced Raman scattered response provides molecular level detail of the
interactions governing recognition by the protein. In concert, our methodologies provide a new approach to
monitoring protein binding to putative drugs in living cells, and to characterize targeting specificity.
The specific aims of this proposal are:
 1) Screen the targeting specificity of peptide-functionalized nanoparticles in live cells.
 2) Develop super-resolution SERS imaging to improve binding specificity studies and identify
 particle location in cells.
 3) Combine non-standard quantum and numerical simulations with experiments to identify key
 motifs in amino acid conformation related to peptide binding.
Overall, the technology and platform we propose will address the challenge of obtaining chemical information
from ligands binding to receptor proteins in intact cells. These studies will provide new insights into the
molecular interactions that regulate signaling pathways and how anomalies in these interactions are
associated with disease and treatment.

## Key facts

- **NIH application ID:** 10122121
- **Project number:** 2R01GM109988-07A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Zachary Schultz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,407
- **Award type:** 2
- **Project period:** 2015-04-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122121

## Citation

> US National Institutes of Health, RePORTER application 10122121, Enhanced Raman Imaging of Ligand-Receptor Recognition (2R01GM109988-07A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122121. Licensed CC0.

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