# Developing lipopolysaccharide-neutralizing peptides through modular high throughput screening strategies

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $68,034

## Abstract

Abstract
Gram-negative bacterial infections account for more than half a million severe sepsis cases every year in the
United States, where a major pathogenic factor is lipopolysaccharides (LPS) and their corresponding toxic
component, lipid A. Minimizing serum lipid A level was expected to be an effective therapy for managing severe
sepsis. This hypothesis has been validated in clinical studies. For instance, hemoperfusion methods using
immobilized polymyxin B (PB) to remove circulating LPS have proven beneficial. However, common LPS-
neutralizing agents, such as PB, are highly toxic, therefore have rather restricted therapeutic applications. In
addition, the repertoire of LPS-binding agents is limited by their naturally occurring precursors. On the other hand,
due to the difficulties in targeting the lipid A moiety, de novo discovery of LPS-neutralizing compounds remains
challenging. Herein, a modular screening approach will be implemented to identify lipid A-specific binders form
cyclic peptide libraries. A rhodamine-phenylboronic acid conjugate will be used to stain the polysaccharide part
in LPS, which allows differentiating polysaccharide-specific binders from lipid A-specific ones. Three orthogonal
methods will be employed to validate the affinity and specificity of identified peptides. Further in vitro validations
will be performed on bone marrow-derived macrophages and human peripheral blood mononuclear cells to test
the bioactivity. These cells will be challenged with LPS in conjunction with the peptides and their cytokine
production will be evaluated. Lower cytokine levels indicate better LPS neutralization effects. Ultimately, the goal
is to identify pan-LPS reactive peptides that exhibit high LPS-neutralization capability as well as low cytotoxicity.

## Key facts

- **NIH application ID:** 9928004
- **Project number:** 5R03AI139916-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Min Xue
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,034
- **Award type:** 5
- **Project period:** 2019-05-10 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928004

## Citation

> US National Institutes of Health, RePORTER application 9928004, Developing lipopolysaccharide-neutralizing peptides through modular high throughput screening strategies (5R03AI139916-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928004. Licensed CC0.

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