title: Use of unnatural amino acids to probe structure-activity relationships and mode-of-action of antimicrobial peptides.
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.
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy. atossi@units.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tossi
authors.forename: Marco
authors.initials: M
authors.lastname: Scocchi
authors.forename: Sotir
authors.initials: S
authors.lastname: Zahariev
authors.forename: Renato
authors.initials: R
authors.lastname: Gennaro
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D015335:Molecular Probes; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000890:Anti-Infective Agents; D015335:Molecular Probes; D010455:Peptides