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

Autor(es)

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

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Medicinal Chemistry; v. 62, n. 22, p. 10294-10304, NOV 28 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/03748-9 - Peptídeos antimicrobianos cíclicos: importância da estrutura cíclica no mecanismo de ação de duas diferentes estruturas.
• Beneficiário: Simone Cristina Barbosa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado