Double-Headed Cationic Lipopeptides: An Emerging Class of Antimicrobials

• Main Authors: Izabela Małuch, Oktawian Stachurski, Paulina Kosikowska-Adamus, Marta Makowska, Marta Bauer, Dariusz Wyrzykowski, Aleksandra Hać, Wojciech Kamysz, Milena Deptuła, Michał Pikuła, Emilia Sikorska
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: peptide-lipid conjugate; double-headed lipopeptide; cationic lipopeptide; self-assembly; antimicrobial agent
• Online Access: https://www.mdpi.com/1422-0067/21/23/8944
• ISSN: 1661-6596; 1422-0067

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 (C₁₆) 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 C₁₆, affect biological functions of lipopeptides, their self-assembling propensity, and their mode of action.