LEGO-lipophosphonoxins: length of hydrophobic module affects permeabilizing activity in target membranes of different phospholipid composition

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00581956" target="_blank" >RIV/61388963:_____/24:00581956 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/24:10474669

Result on the web

<a href="https://doi.org/10.1039/D3RA07251G" target="_blank" >https://doi.org/10.1039/D3RA07251G</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3ra07251g" target="_blank" >10.1039/d3ra07251g</a>

Result language

angličtina

Original language name

LEGO-lipophosphonoxins: length of hydrophobic module affects permeabilizing activity in target membranes of different phospholipid composition

Original language description

In the past few decades, society has faced rapid development and spreading of antimicrobial resistance due to antibiotic misuse and overuse and the immense adaptability of bacteria. Difficulties in obtaining effective antimicrobial molecules from natural sources challenged scientists to develop synthetic molecules with antimicrobial effect. We developed modular molecules named LEGO-Lipophosphonoxins (LEGO-LPPO) capable of inducing cytoplasmic membrane perforation. In this structure-activity relationship study we focused on the role of the LEGO-LPPO hydrophobic module directing the molecule insertion into the cytoplasmic membrane. We selected three LEGO-LPPO molecules named C9, C8 and C7 differing in the length of their hydrophobic chain and consisting of an alkenyl group containing one double bond. The molecule with the long hydrophobic chain (C9) was shown to be the most effective with the lowest MIC and highest perforation rate both in vivo and in vitro. We observed high antimicrobial activity against both G+ and G- bacteria with significant differences in LEGO-LPPOs mechanism of action on these two cell types. We observed a highly cooperative mechanism of LEGO-LPPO action on G- bacteria as well as on liposomes resembling G- bacteria. LEGO-LPPO action on G- bacteria was significantly slower compared to G+ bacteria suggesting the role of the outer membrane in affecting the LEGO-LPPOs perforation rate. This notion was supported by the higher sensitivity of the E. coli strain with a compromised outer membrane. Finally, we noted that the composition of the cytoplasmic membrane affects the activity of LEGO-LPPOs since the presence of phosphatidylethanolamine increases their membrane disrupting activity.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

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

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

RSC Advances

ISSN

2046-2069

e-ISSN

2046-2069

Volume of the periodical

14

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

2745-2756

UT code for WoS article

001143519300001

EID of the result in the Scopus database

2-s2.0-85183784620