Alpha-helical antimicrobial peptides—Using a sequence template to guide structure-activity relationship studies |
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Authors: | Igor Zelezetsky |
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Affiliation: | Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, 34127 Trieste, Italy |
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Abstract: | An important class of cytolytic antimicrobial peptides (AMPs) assumes an amphipathic, α-helical conformation that permits efficient interaction with biological membranes. Host defence peptides of this type are widespread in nature, and numerous synthetic model AMPs have been derived from these or designed de novo based on their characteristics. In this review we provide an overview of the ‘sequence template’ approach which we have used to design potent artificial helical AMPs, to guide structure-activity relationship studies aimed at their optimization, and to help identify novel natural AMP sequences. Combining this approach with the rational use of natural and non-proteinogenic amino acid building blocks has allowed us to probe the individual effects on the peptides' activity of structural and physico-chemical parameters such as the size, propensity for helical structuring, amphipathic hydrophobicity, cationicity, and hydrophobic or polar sector characteristics. These studies furthermore provided useful insights into alternative modes of action for natural membrane-active helical peptides. |
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Keywords: | Abu, 2-aminobutyric acid Acp, aminocylcopentanecarboxylic acid Aib, 2-aminoisobutyric acid AMP, antimicrobial peptide Dab, 2,4-diaminobutyric acid Dap, 2,3-diaminopropionic acid Deg, diethylglycine Dpg, dipropylglycine FS, forward scattering HDP, host defence peptide Hse, homoserine MIC, minimum inhibitory concentration Nle, norleucine Nva, norvaline Orn, ornithine SAR, structure-activity relationship SEM, scanning electron microscopy SS, side scattering TFE, trifluoroethanol |
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