Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli β sliding clamp

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378271%3A_____%2F25%3A00618802" target="_blank" >RIV/68378271:_____/25:00618802 - isvavai.cz</a>

Výsledek na webu

<a href="https://hdl.handle.net/11104/0365821" target="_blank" >https://hdl.handle.net/11104/0365821</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2025.118139" target="_blank" >10.1016/j.bmc.2025.118139</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli β sliding clamp

Popis výsledku v původním jazyce

Bacterial β sliding clamp (β-clamp) is an emerging drug target currently lacking small-molecule inhibitors with good in vivo activity. Thus, there is a need for fast and simple screening methods for identifying inhibitor candidates. Here we demonstrate the use of nuclear magnetic resonance spectroscopy (NMR) for evaluating compound binding to the E. coli β-clamp. To identify suitable molecular probes, a series of tetrahydrocarbazoles were synthesized, some of which contain fluorine. Key challenges in the synthesis were formation of regioisomers during the Fischer indole reaction and reducing racemization at the stereogenic center. The tetrahydrocarbazoles were assayed against the E. coli β-clamp by saturation-transfer difference (STD) NMR, waterLOGSY and T1ρ.

Název v anglickém jazyce

Synthesis and evaluation of fluorinated tetrahydrocarbazoles as probes in NMR based binding assay of the E. coli β sliding clamp

Popis výsledku anglicky

Bacterial β sliding clamp (β-clamp) is an emerging drug target currently lacking small-molecule inhibitors with good in vivo activity. Thus, there is a need for fast and simple screening methods for identifying inhibitor candidates. Here we demonstrate the use of nuclear magnetic resonance spectroscopy (NMR) for evaluating compound binding to the E. coli β-clamp. To identify suitable molecular probes, a series of tetrahydrocarbazoles were synthesized, some of which contain fluorine. Key challenges in the synthesis were formation of regioisomers during the Fischer indole reaction and reducing racemization at the stereogenic center. The tetrahydrocarbazoles were assayed against the E. coli β-clamp by saturation-transfer difference (STD) NMR, waterLOGSY and T1ρ.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10302 - Condensed matter physics (including formerly solid state physics, supercond.)

Projekt

—

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

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

1464-3391

Svazek periodika

122

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

118139

Kód UT WoS článku

001439614100001

EID výsledku v databázi Scopus

2-s2.0-85219132178