Double-Headed Cationic Lipopeptides: An Emerging Class of Antimicrobials

• Published in: International journal of molecular sciences Vol. 21; no. 23; p. 8944
• Main Authors: Małuch, Izabela, Stachurski, Oktawian, Kosikowska-Adamus, Paulina, Makowska, Marta, Bauer, Marta, Wyrzykowski, Dariusz, Hać, Aleksandra, Kamysz, Wojciech, Deptuła, Milena, Pikuła, Michał, Sikorska, Emilia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.11.2020; MDPI
• Subjects: Amino Acid Sequence - genetics; Antiinfectives and antibacterials; antimicrobial agent; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Bacteria; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Candida albicans - drug effects; Candida albicans - pathogenicity; cationic lipopeptide; Chains; Chemical compounds; Cytotoxicity; double-headed lipopeptide; Drug resistance; E coli; Escherichia coli - drug effects; Fatty acids; Gram-positive bacteria; Homology; Humans; Hydrocarbons; Lipopeptides; Lipopeptides - chemistry; Lipopeptides - genetics; Lipopeptides - pharmacology; Membranes; Microbial Sensitivity Tests; Mycoses - drug therapy; Mycoses - microbiology; Palmitic acid; Pathogens; peptide-lipid conjugate; Peptides; Pharmacodynamics; Pharmacokinetics; Pharmacology; Reptiles & amphibians; Residues; Self-assembly; Spectrum analysis; Structure-Activity Relationship; Surfactants; peptide-lipid conjugate; self-assembly; antimicrobial agent; double-headed lipopeptide; cationic lipopeptide
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21238944

Antimicrobial peptides (AMPs) constitute a promising tool in the development of novel therapeutic agents useful in a wide range of bacterial and fungal infections. Among the modifications improving pharmacokinetic and pharmacodynamic characteristics of natural AMPs, an important role is played by lipidation. This study focuses on the newly designed and synthesized lipopeptides containing multiple Lys residues or their shorter homologues with palmitic acid (C ) attached to the side chain of a residue located in the center of the peptide sequence. The approach resulted in the development of lipopeptides representing a model of surfactants with two polar headgroups. The aim of this study is to explain how variations in the length of the peptide chain or the hydrocarbon side chain of an amino acid residue modified with C , affect biological functions of lipopeptides, their self-assembling propensity, and their mode of action.