LEGO-Lipophosphonoxins: A Novel Approach in Designing Membrane Targeting Antimicrobials

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00559721" target="_blank" >RIV/61388963:_____/22:00559721 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/22:00559721 RIV/00216208:11310/22:10446101 RIV/61989592:15110/22:73616810
Result on the web
<a href="https://doi.org/10.1021/acs.jmedchem.2c00684" target="_blank" >https://doi.org/10.1021/acs.jmedchem.2c00684</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.2c00684" target="_blank" >10.1021/acs.jmedchem.2c00684</a>

Result language
angličtina
Original language name
LEGO-Lipophosphonoxins: A Novel Approach in Designing Membrane Targeting Antimicrobials
Original language description
The alarming rise of bacterial antibiotic resistance requires the development of new compounds. Such compounds, lipophosphonoxins (LPPOs), were previously reported to be active against numerous bacterial species, but serum albumins abolished their activity. Here we describe the synthesis and evaluation of novel antibacterial compounds termed LEGO-LPPOs, loosely based on LPPOs, consisting of a central linker module with two attached connector modules on either side. The connector modules are then decorated with polar and hydrophobic modules. We performed an extensive structure-activity relationship study by varying the length of the linker and hydrophobic modules. The best compounds were active against both Gram-negative and Gram-positive species including multiresistant strains and persisters. LEGO-LPPOs act by first depleting the membrane potential and then creating pores in the cytoplasmic membrane. Importantly, their efficacy is not affected by the presence of serum albumins. Low cytotoxicity and low propensity for resistance development demonstrate their potential for therapeutic use.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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