# Targeted Macromolecular Antimicrobial Prodrugs Against Pseudomonas Aeruginosa

> **NIH NIH R21** · CORNELL UNIVERSITY · 2021 · $231,674

## Abstract

The World Health Organization lists Pseudomonas aeruginosa (P. aeruginosa) as a critical priority 1 pathogen
and the Center for Disease Control has it listed at a threat level of “serious” because it has become a severe
threat for hospitalized and immune-compromised patients. P. aeruginosa is a common cause of infections
including pneumonia, bacteremia, urinary tract infections, and surgical site infections. Drug resistance in this
pathogenic organism has grown significantly in the last decade and infections with P. aeruginosa pose a
significant threat to public health and national security. The proposed research seeks to develop a new class of
LecB targeted PEGylated antimicrobial prodrugs that can safely clear infections caused by P. aeruginosa. This
research effort directly addresses a critical barrier to progress in the field of antimicrobial polymers –
mitigating their systemic toxicity brought about by their non-specific mode of action and improving their
biofilm penetration. To address this critical selectivity problem that plagues all antimicrobial polymers,
including new sequence-defined synthetic antimicrobial oligothioetheramides (oligoTEAs) made in our
laboratory, we propose the synthesis of targeted macromolecular prodrugs that actively target Pseudomonas
aeruginosa (P. aeruginosa) and release the active antimicrobial oligoTEA only in the presence of virulence
factors emitted by P. aeruginosa. This mechanism of action, similar to that used in the field of antibody-drug
conjugates, should decrease toxicity due to non-specific exposure while maintaining the potency of the
antimicrobial oligoTEA at the site of infection. In addition to minimizing toxicity, the PEG on the prodrug will
also facilitate biofilm penetration thus further improving activity of the oligoTEAs in a biofilm. The
development of new classes of antibacterial compounds that can eradicate multi-drug resistant P. aeruginosa
will be of immense benefit, particularly for hospitalized and immune-compromised patients. The impact of this
effort cannot be overstated given the current era of accelerated antibiotic resistance.

## Key facts

- **NIH application ID:** 10242726
- **Project number:** 5R21AI154102-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Christopher Akinleye Alabi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,674
- **Award type:** 5
- **Project period:** 2020-08-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242726

## Citation

> US National Institutes of Health, RePORTER application 10242726, Targeted Macromolecular Antimicrobial Prodrugs Against Pseudomonas Aeruginosa (5R21AI154102-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242726. Licensed CC0.

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