title: Design and synthesis of cationic Aib-containing antimicrobial peptides: conformational and biological studies.
abstract: Development of antimicrobial peptides has attracted considerable attention in recent years due to the excessive use of antibiotics, which has led to multiresistant bacteria. Cationic amphiphilic Aib-containing peptide models Ac-(Aib-Arg-Aib-Leu)(n)-NH2, n = 1-4, and sequential cationic polypeptides (Arg-X-Gly)(n), X = Ala, Val, Leu, were prepared and studied for their antimicrobial and hemolytic activity, as well as for their proteolytic stability. Ac-(Aib-Arg-Aib-Leu)(n)-NH2, n = 2, 3 and the polypeptide (Arg-Leu-Gly)(n) exhibited significant antimicrobial activity, and they were nontoxic at their MIC values and resistant, in particular the Aib-peptide models, to enzymatic degradation. The conformational characteristics of the peptide models were studied by circular dichroism (CD). Structure-activity relationship studies revealed the importance of the amphipathic alpha-helical conformation of the reported peptides in inducing antimicrobial effects. It is concluded that peptide models comprising cationic amino acids (Arg), helicogenic and noncoding residues (Aib) and/or hydrophobic and helix-promoting components (Leu) may lead to the development of antimicrobial therapeutics.
authors.affiliation: Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Zikou
authors.forename: Anna-Irini
authors.initials: AI
authors.lastname: Koukkou
authors.forename: Panorea
authors.initials: P
authors.lastname: Mastora
authors.forename: Maria
authors.initials: M
authors.lastname: Sakarellos-Daitsiotis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sakarellos
authors.forename: Constantin
authors.initials: C
authors.lastname: Drainas
authors.forename: Eygenia
authors.initials: E
authors.lastname: Panou-Pomonis
mesh_terms: D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002942:Circular Dichroism; D015195:Drug Design; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation
chemical_list: D000621:Aminoisobutyric Acids; D000890:Anti-Infective Agents; D009842:Oligopeptides