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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Structure-activity analysis of SMAP-29, a sheep leukocytes-derived antimicrobial peptide
1Department of Life Science, Kwangju Institute of Science and Technology, Kwangju, 500-712, Korea.
Abstract:
SAMP-29 is a cathelecidin-derived antimicrobial peptide deduced from sheep myeloid mRNA. To elucidate the structural-activity relationship of SMAP-29, several analogues were synthesized and their antibiotic activity was investigated. Compared to parental SMAP-29, SMAP-29(1-17) and [K(22,25,27)]-SMAP-29 retained relatively effective antimicrobial activity (MIC: 1.0-8.0 microM), but resulted in a complete loss of hemolytic activity. Pro-19 --> Ala substitution ([A19]-SMAP-29) in SMAP-29 induced a significant reduction in antibacterial activity. These results suggested that the N-terminal amphipathic alpha-helical region and the C-terminal hydrophobic region of SMAP-29 are responsible for antimicrobial activity and hemolytic activity, respectively, and the central Pro-19 in SMAP-29 plays a critical role in showing improved antibacterial activity. In particular, [K(2,7,13)]-SMAP-29(1-17) showed potent antimicrobial activity under high salt conditions without hemolytic activity. Thus, this short peptide could serve as an attractive candidate for the development of therapeutic antimicrobial drugs. Structural analysis by circular dichroism suggested that SMAP-29 seems to adopt a helix-bend/turn-extended random conformation.
Insights
Sheep antimicrobial peptide SMAP-29 analogues were synthesized to understand structure-activity relationships. Modified peptides showed reduced hemolytic activity while retaining antimicrobial efficacy, suggesting therapeutic potential.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity.
- Cathelicidins, like SMAP-29, are a class of AMPs with therapeutic potential.
- Understanding the structure-activity relationship (SAR) of AMPs is key for drug development.
Purpose of the Study:
- To investigate the SAR of sheep antimicrobial peptide SMAP-29.
- To identify key structural regions responsible for antimicrobial and hemolytic activities.
- To develop SMAP-29 analogues with improved therapeutic profiles.
Main Methods:
- Synthesis of SMAP-29 analogues.
- Antimicrobial activity assays (MIC determination).
- Hemolytic activity assays.
- Circular dichroism spectroscopy for structural analysis.
Main Results:
- SMAP-29 analogues [SMAP-29(1-17) and [K(22,25,27)]-SMAP-29] retained antimicrobial activity but lost hemolytic activity.
- [A19]-SMAP-29 showed reduced antibacterial activity, indicating the importance of Pro-19.
- The N-terminal helical and C-terminal hydrophobic regions are critical for antimicrobial and hemolytic activities, respectively.
- [K(2,7,13)]-SMAP-29(1-17) demonstrated potent antimicrobial activity under high salt conditions without hemolysis.
Conclusions:
- The N-terminal amphipathic alpha-helical region and C-terminal hydrophobic region of SMAP-29 dictate its antimicrobial and hemolytic activities.
- Pro-19 is crucial for SMAP-29's potent antibacterial activity.
- Modified SMAP-29 peptides, particularly [K(2,7,13)]-SMAP-29(1-17), are promising candidates for developing therapeutic antimicrobial drugs with reduced toxicity.
