Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 9; p. 1430
• Main Authors: Molchanova, Natalia, Hansen, Paul R, Franzyk, Henrik
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.08.2017; MDPI
• Subjects: Alanine; Alkylation; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial peptides; Bacteria; Bacteria - drug effects; Biological activity; Cytotoxicity; Design optimization; Design standards; Drug development; Drugs; Global health; Glycine; Half-Life; Hybrids; Linkages; Microbial Sensitivity Tests; Modular structures; Molecular Structure; Multidrug resistance; Peptides; Peptidomimetics; Peptidomimetics - chemical synthesis; Peptidomimetics - chemistry; peptoids; Review; Selectivity; Side effects; Structural stability; peptidomimetics; peptoids; antibiotics; antimicrobial peptides
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22091430

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. Antimicrobial peptidomimetics mimic the structure and biological activity of AMPs, but display extended stability in the presence of biological matrices. In the present review, focus is on the developments reported in the last decade with respect to their design, synthesis, antimicrobial activity, cytotoxic side effects as well as their potential applications as anti-infective agents. Specifically, only peptidomimetics with a modular structure of residues connected via amide linkages will be discussed. These comprise the classes of α-peptoids ( -alkylated glycine oligomers), β-peptoids ( -alkylated β-alanine oligomers), β³-peptides, α/β³-peptides, α-peptide/β-peptoid hybrids, α/γ -acylated -aminoethylpeptides (AApeptides), and oligoacyllysines (OAKs). Such peptidomimetics are of particular interest due to their potent antimicrobial activity, versatile design, and convenient optimization via assembly by standard solid-phase procedures.