# Designing peptides to block Ara h 2 and Ara h 6 from binding to IgE

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $194,098

## Abstract

Project Summary:
IgE-mediated food allergy, particularly to peanuts (PN) and tree nuts (TN), is a major health
problem in the United States, affecting approximately 4% of children and up to 2% of adults.
Most children allergic to PN do not outgrow this condition and as many as half of these must
also avoid other foods, particularly TN, such as walnuts (WN) and cashew nuts (CN). Recent
progress with early administration of peanuts should reduce new cases of severe although
there are limitations such as compliance. Oral immunotherapy (OIT), sublingual
immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), although not yet FDA
approved, hold significant promise. Subcutaneous injection of omalizumab (anti-IgE; Xolair®)
appears to be a useful adjunct for decreasing reactivity during OIT. Unfortunately, these
approaches are not successful for all patients and, even when successful, have limitations
regarding compliance and unpredictable breakthrough. Thus, there is a significant, unmet
need for new oral treatments, used alone or in combination with those now in development.
We propose to develop novel peptides that mimic conformational epitopes and to bind to Ara h
2 and Ara h 6 for the purposes of inhibiting binding of IgE and potentially for immunotherapy.
Among the 17 known PN allergens, the 2S albumins Ara h 2 and Ara h 6 are the most potent
for eliciting IgE-mediated mast cell activation. Our overarching concept is that we can use
current and evolving knowledge of the molecular details of how these potent allergens elicit an
allergic reaction and advances in the design of stable structured peptides, to develop novel
therapies, and to identify mechanisms whereby allergens interact with IgE. We will present
evidence that there are key IgE-binding, linear and conformational epitopes of Ara h 2 and Ara
h 6. We hypothesize that these epitopes can be targeted using a molecular approach. We
propose design a set of novel linear and 3D mimetic peptides that high affinity for allergen-
specific IgE, low affinity for IgG4 and the ability to interfere with IgE/IgE receptor cross-linking.
These stable, high affinity peptides can ultimately be used for desensitization and potentially for
direct therapy, either alone or in combination with existing approaches (e.g. OIT or EPIT).

## Key facts

- **NIH application ID:** 9823837
- **Project number:** 5R21AI135397-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** STEPHEN C DRESKIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,098
- **Award type:** 5
- **Project period:** 2018-11-16 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823837

## Citation

> US National Institutes of Health, RePORTER application 9823837, Designing peptides to block Ara h 2 and Ara h 6 from binding to IgE (5R21AI135397-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9823837. Licensed CC0.

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