Poly(ethylene Glycol)‐Based Peptidomimetics (Pegtides) of Antimicrobial Peptides

Polyethylene glycol (PEG) is commonly used to improve the pharmacokinetics and pharmacodynamics of therapeutic candidates by conjugation. Here PEG is exploited for peptidomimetic conversion of antimicrobial peptides (AMPs), as candidate antibacterial agents, by replacing their polyamide backbone. The pegtides obtained thereby can be readily synthesized from inexpensive starting materials and demonstrate properties commensurate of AMP mimetics.

Cationic amphipathic poly(ethylene glycol)-based polymers are generated with synthetic efficiencies allowing their evaluation as antimicrobial peptide (AMP) mimetics. Accordingly, statistical copolymers with cationic units consistently functionalized with guanyl groups, but different side-chain lengths, and hydrophobic units displaying long aliphatic, branched, and/or aromatic side chains are produced and tested for their antimicrobial and hemolytic properties. The results obtained indicate that candidates with activities and selectivity commensurate to some AMPs can be obtained and that further development of this novel type of antimicrobial peptidomimetics, pegtides, is warranted for clinical and/or biotechnological applications.

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