# Macrocyclic Peptide Modulators of Protein Function

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $284,101

## Abstract

Macrocyclic Peptide Modulators of Protein Function
Progress toward an understanding of protein-mediated interactions involved in cell physiology and disease
heavily relies on the availability of chemical agents capable of targeting and modulating protein function with
high potency and selectivity. While small-molecule agents have provided a major source of chemical probes and
therapeutics, an overwhelming fraction of human proteins and protein-mediated interactions remains impervious
to modulation using this class of molecules, posing a fundamental barrier to efforts directed at elucidating their
role in physiopathological processes and assessing their therapeutic potential. Our group has recently introduced
an efficient and highly versatile methodology for generating small-size, genetically encoded macrocyclic peptides
in living cells and demonstrated the effectiveness of these 'natural product-like' compounds to disrupt a
challenging protein-protein interaction with high potency and specificity. In this project, this versatile methodology
for macrocyclic peptide synthesis will be integrated with phage display and cell-based selection systems in order
to implement powerful, high-throughput platforms for the rapid discovery of potent and selective macrocyclic
peptide modulators of proteins and protein-protein interactions. Successful completion of this research is
expected to make available new, efficient, and readily accessible technologies useful for developing
macrocyclic peptide agents capable of modulating protein function with high potency and selectivity
across a wide range of target proteins and cellular processes. As such, these technologies are bound to
streamline the development of chemical probes for interrogating cellular pathways and validating therapeutic
targets, the generation of selective reagents for protein detection and labeling, and the identification of potential
lead structures for drug development, thereby accelerating efforts in basic biomedical research, chemical
biology, and drug discovery.

## Key facts

- **NIH application ID:** 10000964
- **Project number:** 5R01GM134076-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Rudi Fasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $284,101
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000964

## Citation

> US National Institutes of Health, RePORTER application 10000964, Macrocyclic Peptide Modulators of Protein Function (5R01GM134076-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000964. Licensed CC0.

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