Design of novel peptide analogs with potent fungicidal activity, based on PMAP-23 antimicrobial peptide isolated from porcine myeloid

Dong Gun Lee, Pyung Il Kim, Yoonkyung Park, Eun Rhan Woo, Ji Suk Choi, Cheol Hee Choi, Kyung Soo Hahm

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

PMAP-23 is a 23-mer peptide derived from porcine myeloid. To develop novel antifungal peptides useful as therapeutic drugs, it would require a strong fungicidal activity against pathogenic fungal cells. To this goal, several analogs, with amino acid substitutions, were designed to increase the net hydrophobicity by Trp (W)-substitution at positions 10, 13, or 14 at the hydrophilic face of PMAP-23 without changing the hydrophobic helical face. The Trp (W)-substitution (P6) showed an enhanced fungicidal and antitumor activities, with the fungicidal activity inhibited by salts and the respiratory inhibitor, NaN3. The results suggested that the increase of hydrophobicity of the peptides correlated with fungicidal activity. The fungicidal effects of analog peptides were further investigated using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane probe. In Candida albicans, the analog peptide (P6) exerted its fungicidal effect on the blastoconidia in 20% fetal bovine serum by disrupting the mycelial forms. Furthermore, P6 caused significant morphological changes, and these facts suggested that the fungicidal function of the novel analog peptide (P6) was by damaging the fungal cell membranes. Thus, this peptide may provide a useful template for designing novel antifungal peptides useful for the treatment of infectious diseases.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume293
Issue number1
DOIs
StatePublished - 26 Apr 2002

Keywords

  • Analog peptides
  • Antifungal peptides
  • Hydrophobicity
  • PMAP-23

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