Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/88754
Title: Design and Syntheses of Highly Potent Teixobactin Analogues against Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococci (VRE) in Vitro and in Vivo
Authors: Parmar, Anish
Lakshminarayanan, Rajamani
Iyer, Abhishek
Mayandi, Venkatesh
Goh, Eunice Tze Leng
Lloyd, Daniel G.
Chalasani, Madhavi Latha Somaraju
Verma, Navin Kumar
Prior, Stephen H.
Beuerman, Roger W.
Madder, Annemieke
Taylor, Edward J.
Singh, Ishwar
Keywords: Bacterial Infection
Teixobactin
Issue Date: 2018
Source: Parmar, A., Lakshminarayanan, R., Iyer, A., Mayandi, V., Goh, E. T. L., Lloyd, D. G., et al. (2018). Design and Syntheses of Highly Potent Teixobactin Analogues against Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococci (VRE) in Vitro and in Vivo. Journal of Medicinal Chemistry, 61(5), 2009-2017.
Series/Report no.: Journal of Medicinal Chemistry
Abstract: The cyclic depsipeptide, teixobactin, kills a number of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium tuberculosis without detectable resistance. To date, teixobactin is the only molecule in its class that has shown in vivo antibacterial efficacy. In this work, we designed and synthesized 10 new in vivo ready teixobactin analogues. These analogues showed highly potent antibacterial activities against Staphylococcus aureus, MRSA, and vancomycin-resistant enterococci (VRE) in vitro. One analogue, d-Arg4-Leu10-teixobactin, 2, was found to be noncytotoxic in vitro and in vivo. Moreover, topical instillation of peptide 2 in a mouse model of S. aureus keratitis decreased the bacterial bioburden (>99.0% reduction) and corneal edema significantly as compared to untreated mouse corneas. Collectively, our results have established the high therapeutic potential of a teixobactin analogue in attenuating bacterial infections and associated severities in vivo.
URI: https://hdl.handle.net/10356/88754
http://hdl.handle.net/10220/44693
ISSN: 0022-2623
DOI: 10.1021/acs.jmedchem.7b01634
Rights: © 2018 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Medicinal Chemistry, American Chemical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1021/acs.jmedchem.7b01634].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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