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Development of teixobactin analogues containing hydrophobic, non-proteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms.
Parmar, Anish; Lakshminarayanan, Rajamani; Iyer, Abhishek; Goh, Eunice Tze Leng; To, Tsz Ying; Yam, Joey Kuok Hoong; Yang, Liang; Newire, Enas; Robertson, Maria C; Prior, Stephen H; Breukink, Eefjan; Madder, Annemieke; Singh, Ishwar.
Afiliación
  • Parmar A; Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, L7 8TX, UK; Antimicrobial Drug Discovery and Development, Depar
  • Lakshminarayanan R; Singapore Eye Research Institute, The Academia, Discovery Tower Level 6, 20 College Road, 169857, Singapore.
  • Iyer A; Organic and Biomimetic Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 (S4), B-9000, Ghent, Belgium.
  • Goh ETL; Singapore Eye Research Institute, The Academia, Discovery Tower Level 6, 20 College Road, 169857, Singapore.
  • To TY; Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, L7 8TX, UK; Antimicrobial Drug Discovery and Development, Depar
  • Yam JKH; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 637551, Singapore.
  • Yang L; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 637551, Singapore; School of Biological Sciences, Division of Structural Biology and Biochemistry, Nanyang Technological University, 639798, Singapore.
  • Newire E; Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, L7 8TX, UK; Antimicrobial Drug Discovery and Development, Depar
  • Robertson MC; Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, L7 8TX, UK; Antimicrobial Drug Discovery and Development, Depar
  • Prior SH; School of Chemistry, Joseph Banks Laboratories, University of Lincoln, Green Lane, Lincoln, LN6 7DL, United Kingdom.
  • Breukink E; Department of Membrane Biochemistry and Biophysics, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584, CH, Utrecht, the Netherlands.
  • Madder A; Organic and Biomimetic Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 (S4), B-9000, Ghent, Belgium.
  • Singh I; Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, William Henry Duncan Building, 6 West Derby St, Liverpool, L7 8TX, UK; Antimicrobial Drug Discovery and Development, Depar
Eur J Med Chem ; 261: 115853, 2023 Dec 05.
Article en En | MEDLINE | ID: mdl-37857144
Teixobactin is a cyclic undecadepsipeptide that has shown excellent potency against multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). In this article, we present the design, synthesis, and antibacterial evaluations of 16 different teixobactin analogues. These simplified analogues contain commercially available hydrophobic, non-proteogenic amino acid residues instead of synthetically challenging expensive L-allo-enduracididine amino acid residue at position 10 together with different combinations of arginines at positions 3, 4 and 9. The new teixobactin analogues showed potent antibacterial activity against a broad panel of Gram-positive bacteria, including MRSA and VRE strains. Our work also presents the first demonstration of the potent antibiofilm activity of teixobactin analogoues against Staphylococcus species associated with serious chronic infections. Our results suggest that the use of hydrophobic, non-proteogenic amino acids at position 10 in combination with arginine at positions 3, 4 and 9 holds the key to synthesising a new generation of highly potent teixobactin analogues to tackle resistant bacterial infections and biofilms.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus Resistente a Meticilina / Enterococos Resistentes a la Vancomicina Idioma: En Revista: Eur J Med Chem Año: 2023 Tipo del documento: Article Pais de publicación: Francia
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus Resistente a Meticilina / Enterococos Resistentes a la Vancomicina Idioma: En Revista: Eur J Med Chem Año: 2023 Tipo del documento: Article Pais de publicación: Francia