# Transmembrane peptides for targeting acidosis

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2020 · $328,680

## Abstract

PROJECT SUMMARY
 Targeted therapies are based on diseased cells having characteristics that distinguish them from healthy
cells. Several pathological states including cancer, ischemia, and inflammation are characterized by acidosis.
We propose to exploit acidosis to develop new technologies for targeted therapies. We have recently
developed new peptides that insert into membranes only in acidic conditions. Preliminary data show that these
acidity-triggered rational membrane (ATRAM) peptides have favorable biophysical properties and target cells
in a pH-responsive fashion. We will determine the optimal peptide sequence in the context of the transverse
asymmetry in lipid composition found in most cellular membranes. Next, we will determine the pKa of the
residues responsible for triggering membrane insertion under acidic conditions. This will be instrumental in
elucidating the molecular mechanism of ATRAM peptides. We have evolved the design of the ATRAM
peptides to design bifunctional peptides that have the potential to modulate the activity of the EphA2 receptor.
EphA2 is involved in mediating invasion and metastasis in different tumor types. Our data suggest that these
peptides are soluble, but are also able to insert into membranes and activate the EphA2 receptor. We will
study peptide control over the clustering of the EphA2 receptor. A set of peptides of different sequences will be
used as a tool to determine the conformational changes associated to the formation of the membrane clusters
of EphA2, leading to receptor activation. This multidisciplinary study will lead to a molecular understanding of
the mode of action of these peptides. This knowledge will provide important clues to develop future therapeutic
technologies that specifically target the acidosis of diseased tissues.

## Key facts

- **NIH application ID:** 10000940
- **Project number:** 5R01GM120642-05
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** Francisco Nicolas Barrera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,680
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000940

## Citation

> US National Institutes of Health, RePORTER application 10000940, Transmembrane peptides for targeting acidosis (5R01GM120642-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000940. Licensed CC0.

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