# A NOVEL APPROACH FOR DRUGS TO CANDIDA ALBICANS

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE KNOXVILLE · 1987 · $185,921

## Abstract

Fungal infections are responsible for a large portion of opportunistic
infections in compromised hosts.  Among the fungi, Candida albicans is one
of the most prevalent agents causing secondary disease in patients weakened
by cancer, immunosuppressive therapy, radiation treatment, and other
debilitating conditions such as acquired immunodeficiency syndrome (AIDS).
The currently used anticandidal drugs suffer from significant clinical
limitations.  We propose to take advantage of the biochemical difference
between the cell envelopes of Candida and mammalian tissue to design drugs
specific for this pathogenic yeast.  In particular, we will adapt the
polyoxins for use against medically important fungi.  Since polyoxins are
non-toxic to mammals and inhibit chitan synthetase, an enzyme essential for
cell wall biosynthesis in fungi and invertebrates but absent from mammals,
our drugs will be pathogen specific.  Synthetic analogs of polyoxin L
previously prepared in our laboratory inhibit chitin synthetase from C.
albicans at micromolar concentrations.  These peptidyl nucleosides also
kill this yeast at millimolar concentrations in culture.  The quantitative
difference between the in vitro and in vivo activity of the synthetic
polyoxins is a consequence of the poor permeation by the compounds into
yeast and their degradation by intracellular peptidases.  We will overcome
the instability of the synthetic polyoxins toward peptidases by preparing
molecules containing N-alkyl amino acide residues, dehydroamino acids, or
peptide bond analogs such as ester, phosphonamide, and aminoxy moieties.
The poor permeation of the polyoxins will be overcome by the attachment of
lipophilic groups and peptide carriers to parts of the drug not necessary
for activity.  All modifications will be based on structure-function
relationships that we have defined for the peptide transport system and
chitin synthetase of C. albicans.  The synthetic polyoxins will be examined
against chitin synthetase in vitro and for their ability to alter the
morphology and growth of C. albicans in culture.  Based on our in vitro
results, an established mouse model system will be used to evaluate
promising candidates.  This project should provide insights into the
biosynthesis of cell wall components in C. albicans and may yield drugs
against a variety of fungal patheogens.

## Key facts

- **NIH application ID:** 3125730
- **Project number:** 5R01AI014387-09
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **SAM.gov UEI:** FN2YCS2YAUW3
- **Principal Investigator:** JEFFREY M. BECKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $185,921
- **Award type:** 5
- **Project period:** 1977-09-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125730

## Citation

> US National Institutes of Health, RePORTER application 3125730, A NOVEL APPROACH FOR DRUGS TO CANDIDA ALBICANS (5R01AI014387-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125730. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*