title: Design of novel peptide analogs with potent fungicidal activity, based on PMAP-23 antimicrobial peptide isolated from porcine myeloid.
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, NaN(3). 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.
authors.affiliation: Research Center for Proteineous Materials, Chosun University, 375 Seosuk-Dong, Dong-Ku, Kwangju 501-759, Republic of Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
authors.forename: Pyung Il
authors.initials: PI
authors.lastname: Kim
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Ji Suk
authors.initials: JS
authors.lastname: Choi
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Choi
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Hahm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C086301:porcine myeloid antibacterial peptide 23