Design and synthesis of cationic Aib-containing antimicrobial peptides: conformational and biological studies.
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.
Zikou
Sofia
S
Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Koukkou
Anna-Irini
AI
Mastora
Panorea
P
Sakarellos-Daitsiotis
Maria
M
Sakarellos
Constantinos
C
Drainas
Constantin
C
Panou-Pomonis
Eygenia
E
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
D000621:Aminoisobutyric Acids; D000890:Anti-Infective Agents; D009842:Oligopeptides