Parmar, Anish, Lakshminarayanan, Rajamani, Iyer, Abhishek, Goh, Eunice Tze Leng, To, Tsz Ying 
ORCID: 0009-0001-3624-9129, Yam, Joey Kuok Hoong, Yang, Liang, Newire, Enas, Robertson, Maria C, Prior, Stephen H et al (show 3 more authors)
(2023)
Development of teixobactin analogues containing hydrophobic, non-proteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms.
European journal of medicinal chemistry, 261.
115853-.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Biofilms, Amino Acids, Anti-Bacterial Agents, Microbial Sensitivity Tests, Structure-Activity Relationship, Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci |
| Divisions: | Faculty of Health and Life Sciences Faculty of Science and Engineering > School of Physical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Nov 2023 08:51 |
| Last Modified: | 02 Dec 2023 01:14 |
| DOI: | 10.1016/j.ejmech.2023.115853 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3176885 |
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