# Detection of Synaptic Proteins with Fluorescent Molecular Rotor-labeled Peptides

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $188,400

## Abstract

Detection of Synaptic Proteins with Fluorescent Molecular Rotor-labeled Peptides
Abstract
Our goal is to establish routine methodology for development of synthetic peptides for instant and specific
detection of endogenous unmodified proteins in fixed and living neurons. We will screen One Bead One
Compound (OBOC) combinatorial peptide libraries invented by co-investigator (Co-I) Kit Lam (Nature 354, 82-
84) for peptides with fluorescent molecular rotors (FMRs). FMR peptides will fluoresce only when specifically
bound to their target protein but not when free in solution. Initial focus will be on the key postsynaptic proteins
of glutamatergic synapses (AMPARs (AMPA-type glutamate receptors), NMDARs (NMDA-type glutamate
receptors), PSD-95 (anchors AMPARs and NMDARs at postsynaptic sites)). Signal to noise ratio (>2300fold)
and photostability (by ~ 10fold) is superior to current xFP tags. Peptides will be made membrane permeant
with the tat sequence or by myristoylation. This transformative approach will allow detection of proteins within
minutes in living systems circumventing technically complicated, time consuming, and expensive genetic
protein tagging. It will also dramatically accelerate (by 50fold) protein distribution in fixed cells by high and
super-resolution microscop as it will not require the use of primary and secondary antibodies, not even
washing steps. FMR peptides can be easily re-synthesized eliminating the variability inherent to antibody
probes. Peptides will be reiteratively optimized to achive high affinity and specificity. My long-standing and
overarching interest is to determine the molecular mechanisms that govern postsynaptic function (e.g., Science
293,98; Science 293,2205; Science Signaling 10, eaaf9659; Nature 411,801; Neuron 74,1023; Neuron 78,483;
Neuron 81,249; Neuron 88,528; Neuron 97, 1094; Neuron 98, 783; EMBO J. 26,4879; EMBO J. 29,482; EMBO
J. 31,1203; EMBO J. 33,1341; EMBO J. 35,1330; EMBO J. 36,1330; EMBO J. 37, 122). PSD-95 determines
postsynaptic localization of glutamate receptors. Development of FMR-peptides that fluoresce upon specific
binding to these proteins will allow live imaging of their localization and of the dynamic changes synapses with
those proteins undergo over time at resting and stimulated conditions in cultured neurons and ultimately in the
brain in vivo. Ultimately, I envision to develop FMR-peptides for >100 pre- and postsynaptic proteins. Others
will apply our technology inside and outside the CNS in all fields of biomedical research.
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## Key facts

- **NIH application ID:** 9861595
- **Project number:** 1R21MH121618-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JOHANNES W HELL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,400
- **Award type:** 1
- **Project period:** 2019-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861595

## Citation

> US National Institutes of Health, RePORTER application 9861595, Detection of Synaptic Proteins with Fluorescent Molecular Rotor-labeled Peptides (1R21MH121618-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9861595. Licensed CC0.

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