Influence of Non-natural Cationic Amino Acids on the Biological Activity Profile of Innate Defense Regulator Peptides

Evan F. Haney, Simone C. Barbosa, Beverlie Baquir, Robert E.W. Hancock

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12 Citations (Scopus)


Non-natural amino acids can be incorporated into synthetic host defense peptides (HDPs) to modulate their susceptibility to proteolytic degradation. However, the impact of non-natural amino acids on the antibiofilm and immunomodulatory activities of synthetic HDPs remains unclear. Using SPOT-synthesized peptide arrays, non-natural cationic amino acids of varying side chain lengths were incorporated into a synthetic HDP, IDR-1018, and the impact of these substitutions on the antibiofilm activity toward methicillin resistant Staphylococcus aureus biofilms was assessed. Multiply-substituted derivatives were designed that incorporated favorable non-natural cationic amino acid moieties throughout IDR-1018. The antibiofilm and immunomodulatory activities of these derivatives were assessed in vitro, revealing that the incorporation of non-natural amino acids modulated (either positively or negatively) these activities of IDR-1018. Furthermore, the tryptic stability of the IDR-1018 derivatives was assessed revealing that proteolytic stability was favored for shorter cationic side chains and was influenced by the primary peptide sequence.

Original languageEnglish
Pages (from-to)10294-10304
Number of pages11
JournalJournal of medicinal chemistry
Issue number22
Publication statusPublished or Issued - 27 Nov 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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