Naphthylated LEGO-lipophosphonoxin antibiotics used as a fluorescent tool for the observation of target membrane perturbations preceding its disruption

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00600353" target="_blank" >RIV/61388963:_____/25:00600353 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388955:_____/25:00600353 RIV/00216208:11310/25:10488180

Výsledek na webu

<a href="https://doi.org/10.1088/2050-6120/ad8abf" target="_blank" >https://doi.org/10.1088/2050-6120/ad8abf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1088/2050-6120/ad8abf" target="_blank" >10.1088/2050-6120/ad8abf</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Naphthylated LEGO-lipophosphonoxin antibiotics used as a fluorescent tool for the observation of target membrane perturbations preceding its disruption

Popis výsledku v původním jazyce

Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPO) are small synthetic modular peptidomimetics with promising antimicrobial activity. The LEGO-LPPO mechanism of antibacterial action has been determined to be the depolarization and disruption of bacterial membranes. Their modular nature is advantageous for fine tuning their biological properties. In order to optimize the structure of LEGO-LPPO even further, it is important to understand the interaction of LEGO-LPPO with bacterial membranes at the molecular level. In this work, we present the synthesis of five LEGO-LPPO (designated as1_naph2-4-G to5_naph2-4-G) molecules bearing fluorescent naphtylethyl moieties and their usage in the study of LEGO-LPPO behaviour in the membrane. Our goal was to characterize fluorescently labelled LEGO-LPPO under conditions that do not completely disrupt the membrane, mostly in the form of membrane-bound monomers. We observed the intramolecular interactions of hydrophobic modules of1_naph2-4-G in the buffer by detecting dynamic naphthyl excimers and their disappearance after1_naph2-4-G bind into the membranes. In the membrane, the molecule1_naph2-4-G slightly affects the membrane fluidity of DOPG membranes above the phase transition. The naphthyl fluorophore itself has fast and almost unrestricted rotation around ethylene linking groups (rinf= 0.010), which indicates a considerable chaotropic effect of the hydrophobic modules of1_naph2-4-G at the given depth of the membrane.1_naph2-4-G proved to be a useful model for observing the interaction of LEGO-LPPO antibiotics with the phospholipid bilayer enabling us to decipher its effects on membrane state and dynamics, its binding and penetration into the membrane, its structure and the particular depth that it occupies.

Název v anglickém jazyce

Naphthylated LEGO-lipophosphonoxin antibiotics used as a fluorescent tool for the observation of target membrane perturbations preceding its disruption

Popis výsledku anglicky

Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPO) are small synthetic modular peptidomimetics with promising antimicrobial activity. The LEGO-LPPO mechanism of antibacterial action has been determined to be the depolarization and disruption of bacterial membranes. Their modular nature is advantageous for fine tuning their biological properties. In order to optimize the structure of LEGO-LPPO even further, it is important to understand the interaction of LEGO-LPPO with bacterial membranes at the molecular level. In this work, we present the synthesis of five LEGO-LPPO (designated as1_naph2-4-G to5_naph2-4-G) molecules bearing fluorescent naphtylethyl moieties and their usage in the study of LEGO-LPPO behaviour in the membrane. Our goal was to characterize fluorescently labelled LEGO-LPPO under conditions that do not completely disrupt the membrane, mostly in the form of membrane-bound monomers. We observed the intramolecular interactions of hydrophobic modules of1_naph2-4-G in the buffer by detecting dynamic naphthyl excimers and their disappearance after1_naph2-4-G bind into the membranes. In the membrane, the molecule1_naph2-4-G slightly affects the membrane fluidity of DOPG membranes above the phase transition. The naphthyl fluorophore itself has fast and almost unrestricted rotation around ethylene linking groups (rinf= 0.010), which indicates a considerable chaotropic effect of the hydrophobic modules of1_naph2-4-G at the given depth of the membrane.1_naph2-4-G proved to be a useful model for observing the interaction of LEGO-LPPO antibiotics with the phospholipid bilayer enabling us to decipher its effects on membrane state and dynamics, its binding and penetration into the membrane, its structure and the particular depth that it occupies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Methods and Applications in Fluorescence

ISSN

2050-6120

e-ISSN

2050-6120

Svazek periodika

13

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

015001

Kód UT WoS článku

001349710200001

EID výsledku v databázi Scopus

2-s2.0-85208688377