# First-in-class peptide therapeutics for mitochondrial disorders: molecular mechanism of action and optimization of design

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT STORRS · 2023 · $87,512

## Abstract

SUMMARY
 This administrative supplement application (PA-20-272) is for the purchase of a single piece of equipment
to support the research activities of the NIA grant, “First-in-class peptide therapeutics for mitochondrial disorders:
molecular mechanism of action and optimization of design” (R01AG065879). The instrument being sought is a
new research grade spectrofluorometer (Fluorolog-QM-75-22-C, HORIBA Scientific). This will replace the
existing instrument in my laboratory (Fluorolog 3-22), which experienced a catastrophic failure in September
2022 (in the third year of this R01 project period), rendering the instrument inoperable. This current instrument
was purchased in 2008 when I was establishing my laboratory at the University of Connecticut. Although it has
consistently yielded high-quality and reproducible data, in recent years the Fluorolog 3-22 has needed major
repairs with increasing frequency, on a nearly once-yearly basis. Each major repair costs thousands of dollars
and results in extended downtime (typically several weeks) while instrument components are being serviced at
the company. Hence, the cost of maintaining this instrument, in terms of financial burden and productivity loss,
has become too high to manage. Furthermore, the Fluorolog 3-22 model has now been discontinued by HORIBA
and replacement parts (electronics, optics, etc.) are being phased out, meaning that servicing of key instrument
components is becoming impossible. The recent instrument failure occurred this month when the xenon arc lamp
housing power supply failed. Hence, the only option is to acquire a replacement instrument.
 Analytical fluorescence spectroscopy is an essential part of my research program and is central to all
aims of the grant activities under R01AG065879. These fluorescence-based activities include: (i) analysis of the
equilibrium binding properties of peptides and other small molecules with model membranes and mitochondria;
(ii) validation, analysis and quality control of novel, rationally designed mitochondria-targeted compounds as
therapeutic agents for mitochondrial aging; (iii) assays for the effects of therapeutic compounds on membrane
physical properties; (iv) analysis of mitochondrial function and physiological integrity, including membrane
potential, calcium flux and reactive oxygen species production; and (v) evaluation of the effects of mitochondrial
drugs on protein import and amyloid fibril formation on mitochondrial membranes. These measurements require
multiple independent fluorescence techniques (precise emission and excitation spectral scans, anisotropy
readings, Forster resonance energy transfer, static and dynamic quenching) and they are done using complex
samples that contain model membranes, isolated organelles, and cells. This work therefore requires a top quality
spectrofluorometer that can render high-resolution data from samples with complex backgrounds. In this regard,
the Fluorolog-QM-75-22-C will be an excellent rep...

## Key facts

- **NIH application ID:** 10727483
- **Project number:** 3R01AG065879-03S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** NATHAN N ALDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $87,512
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10727483

## Citation

> US National Institutes of Health, RePORTER application 10727483, First-in-class peptide therapeutics for mitochondrial disorders: molecular mechanism of action and optimization of design (3R01AG065879-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10727483. Licensed CC0.

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