Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 61, Issue 5, Pages 2009-2017Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b01634
Keywords
-
Categories
Funding
- University of Lincoln
- Royal Society [UF100116, RG130163, 645684]
- Rosetrees Trust [JS16/M583]
- Singapore National Medical Research Council [NMRC/CBRG/0048/2013]
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore [L0412290]
- Singapore Ministry of Education Academic Research Fund Tier 1 [2015-T1-001-082]
- Rosetrees Trust [M583] Funding Source: researchfish
Ask authors/readers for more resources
The cyclic depsipeptide, teixobactin, kills a number of Grampositive 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-Arg(4)-Leu(10)-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available