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

Author(s)

Haney, Evan F. ^[1] ; Barbosa, Simone C. ^[1] ; Baquir, Beverlie ^[1] ; Hancock, Robert E. W. ^[1]

Affiliation

^[1] Univ British Columbia, Ctr Microbial Dis & Immun Res, Vancouver, BC V6T 1Z4 - Canada

• Document type: Journal article
• Source: Journal of Medicinal Chemistry; v. 62, n. 22, p. 10294-10304, NOV 28 2019.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 14/03748-9 - ANTIMICROBIAL CYCLIC PEPTIDES: THE IMPORTANCE OF CYCLIC STRUCTURE OF THE MECHANISM OF ACTION OF TWO DIFFERENT STRUCTURES.
• Grantee: Simone Cristina Barbosa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral