Abstract
Endogenous antimicrobial peptides (AMPs) can have multimodal mechanisms of bacterial inactivation, such as membrane lysis, interference with cell wall biosynthesis or membrane-based protein machineries, or translocation through the membrane to intracellular targets. The controlled variation of side-chain characteristics in their amino acid residues can provide much useful information on structure–activity relationships and mode-of-action, and also lead to improved activities. The small size and relatively low complexity of AMPs make them amenable to solid-phase peptide synthesis, facilitating the use of nonproteinogenic amino acids and vastly increasing the accessible molecular diversity of side chains. Here, we describe how such residues can be used to modulate such key parameters as cationicity, hydrophobicity, steric factors conformational stability, and H-bonding.
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Abbreviations
- AA:
-
Amino acid
- DBU:
-
1,8-Diazabicyclo[5.4.0]undec-7-ene
- DCM:
-
Dichloromethane
- DIPCDI:
-
Diisopropyl carbodiimide
- DKP:
-
Diketopiperazine
- DMF:
-
N,N-dimethylformamide
- DODT:
-
3,6-Dioxa-1,8-octanedithiol
- EDT:
-
Ethaneditiol
- Fmoc:
-
Fluorenylmethyloxycarbonyl
- HFIP:
-
Hexafluoroisopropanol
- HOBt:
-
Hydroxybenzotriazole
- ivDde:
-
1-(4,4-Dimethyl-2,6-dioxo-cyclohexylidene)-3-methyl-butyl
- Mmt:
-
Monomethoxytrityl
- NMP:
-
N-methylpyrrolidone
- OSu:
-
Succinimidyl carbonate
- PEG-PS:
-
Polyethyleneglycol-polystyrene
- PG:
-
Side-chain protecting group
- PIP:
-
Piperidine
- PyBOP:
-
(Benzotriazol-1-yl-oxy)tripyrrolidinophosphonium hexafluoro phosphate
- s.r.v.:
-
Swelled resin volume
- SPPS:
-
Solid-phase peptide synthesis
- TIPS:
-
Triisopropylsilane
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Acknowledgment
This work was supported by the Friuli Venezia Giulia LR 26 regional grant R3A2.
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Tossi, A., Scocchi, M., Zahariev, S., Gennaro, R. (2012). Use of Unnatural Amino Acids to Probe Structure–Activity Relationships and Mode-of-Action of Antimicrobial Peptides. In: Pollegioni, L., Servi, S. (eds) Unnatural Amino Acids. Methods in Molecular Biology, vol 794. Humana Press. https://doi.org/10.1007/978-1-61779-331-8_10
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DOI: https://doi.org/10.1007/978-1-61779-331-8_10
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