Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.
Bioorg Med Chem
; 106: 117735, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38714021
ABSTRACT
Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes de Sensibilidade Microbiana
/
Peptídeos Catiônicos Antimicrobianos
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Hemólise
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Lisina
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article