Back to Search
Start Over
Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (1), pp. e53326. Date of Electronic Publication: 2013 Jan 11. - Publication Year :
- 2013
-
Abstract
- Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2) terminus of the peptide and the fragment arasin 1(1-23) was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23) were shown to be non-toxic to human red blood cells and arasin 1(1-23) was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23) was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC), arasin 1(1-23) was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23) has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23) involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.
- Subjects :
- Amino Acid Sequence
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Antifungal Agents chemistry
Antifungal Agents pharmacology
Cell Membrane Permeability drug effects
Chitin metabolism
Circular Dichroism
Escherichia coli drug effects
Hemolysis drug effects
Humans
Kinetics
Microbial Sensitivity Tests
Microbial Viability drug effects
Molecular Sequence Data
Peptide Fragments chemistry
Peptide Fragments pharmacology
Peptides chemistry
Peptides pharmacology
Proline-Rich Protein Domains
Structure-Activity Relationship
Anti-Infective Agents chemistry
Anti-Infective Agents pharmacology
Antimicrobial Cationic Peptides chemistry
Antimicrobial Cationic Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23326415
- Full Text :
- https://doi.org/10.1371/journal.pone.0053326