# Control of Facial Amphiphilicity to Tune Macromolecular Interactions with Bacteria

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $365,150

## Abstract

Abstract
 Multidrug-resistant bacteria have evolved into a global crisis on the shortage of available
antibiotics. Facing the mounting pressure, it is essential to discover and design next-generation
portfolios of novel antimicrobial compositions. Nonspecific interactions are among the most
promising approaches for evading antimicrobial resistance. Such interactions include Coulombic
attraction between oppositely charged groups and hydrophobic-hydrophobic interactions. It
involves a series of coordinated and cascade events for antimicrobial agents to attack bacteria.
Because of non-specificity, it would be more challenging for bacteria to develop mechanisms for
resistance. On the other hand, strength and selectivity of such interactions are critical to efficacy
of antimicrobial killing against bacteria as well as cytocompatibility toward eukaryotic cells.
 We propose to design local facial amphiphilicity clustered along a macromolecular chain as a
new class of antimicrobial compositions that are particularly effective against Gram-negative
pathogens. This unique macromolecular composition overcomes many deficiencies of
antimicrobial peptides and antimicrobial polymers. First it adopts the facial amphiphilicity from
host defense peptides, but not necessarily possessing a helical conformation; second it does not
need to overcome a likely impossible global conformational arrangement that antimicrobial
polymers need to adapt to make facial amphiphilicity. This new design of macromolecular
antimicrobials is demonstrated with novel cationic polymers containing a series of multicyclic
natural products including abietic acid, cholic and ursolic acid, which are representatives of tri-,
tetra- and penta-cyclic compounds. We define a facial amphiphilic index (FAI) to understand a
combination of hydrophobicity and charged groups as well as cross-sectional areas that are
needed to penetrate through outer leaflets and further damage cell membranes of bacteria. The
most contribution is to correlate facial amphiphilicity with cell compositions for designing selective
antimicrobial therapies that could pave a new pathway to fighting vexing bacterial resistance.

## Key facts

- **NIH application ID:** 10734759
- **Project number:** 5R01AI149810-05
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Chuanbing Tang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $365,150
- **Award type:** 5
- **Project period:** 2019-12-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734759

## Citation

> US National Institutes of Health, RePORTER application 10734759, Control of Facial Amphiphilicity to Tune Macromolecular Interactions with Bacteria (5R01AI149810-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10734759. Licensed CC0.

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