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A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2016 Mar 10; Vol. 59 (5), pp. 1791-9. Date of Electronic Publication: 2016 Feb 29. - Publication Year :
- 2016
-
Abstract
- New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.
- Subjects :
- Animals
Antimicrobial Cationic Peptides chemical synthesis
Arginine analysis
Arginine chemistry
Candida albicans cytology
Dose-Response Relationship, Drug
Female
HEK293 Cells
Hemolysis drug effects
Humans
Lysine analysis
Lysine chemistry
Mice
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship
Tryptophan analysis
Tryptophan chemistry
Antimicrobial Cationic Peptides chemistry
Antimicrobial Cationic Peptides pharmacology
Candida albicans drug effects
Drug Design
Drug Resistance, Fungal drug effects
Vaginitis drug therapy
Vaginitis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 59
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26881456
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.5b01264