Developing Equipotent Teixobactin Analogues against Drug-Resistant Bacteria and Discovering a Hydrophobic Interaction between Lipid II and Teixobactin.
J Med Chem
; 61(8): 3409-3421, 2018 04 26.
Article
em En
| MEDLINE
| ID: mdl-29629769
ABSTRACT
Teixobactin, targeting lipid II, represents a new class of antibiotics with novel structures and has excellent activity against Gram-positive pathogens. We developed a new convergent method to synthesize a series of teixobactin analogues and explored structure-activity relationships. We obtained equipotent and simplified teixobactin analogues, replacing the l- allo-enduracididine with lysine, substituting oxygen to nitrogen on threonine, and adding a phenyl group on the d-phenylalanine. On the basis of the antibacterial activities that resulted from corresponding modifications of the d-phenylalanine, we propose a hydrophobic interaction between lipid II and the N-terminal of teixobactin analogues, which we map out with our analogue 35. Finally, a representative analogue from our series showed high efficiency in a mouse model of Streptococcus pneumoniae septicemia.
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Base de dados:
MEDLINE
Assunto principal:
Uridina Difosfato Ácido N-Acetilmurâmico
/
Depsipeptídeos
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Antibacterianos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article