Set-up and screening of a fragment library targeting the 14-3-3 protein interface

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00511984" target="_blank" >RIV/67985823:_____/19:00511984 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10403396

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2019/MD/C9MD00215D#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2019/MD/C9MD00215D#!divAbstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c9md00215d" target="_blank" >10.1039/c9md00215d</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Set-up and screening of a fragment library targeting the 14-3-3 protein interface

Popis výsledku v původním jazyce

Protein-protein interactions (PPIs) are at the core of regulation mechanisms in biological systems and consequently became an attractive target for therapeutic intervention. PPIs involving the adapter protein 14-3-3 are representative examples given the broad range of partner proteins forming a complex with one of its seven human isoforms. Given the challenges represented by the nature of these interactions, fragment-based approaches offer a valid alternative for the development of PPI modulators. After having assembled a fragment set tailored on PPIs' modulation, we started a screening campaign on the sigma isoform of 14-3-3 adapter proteins. Through the use of both mono- and bi-dimensional nuclear magnetic resonance spectroscopy measurements, coupled with differential scanning fluorimetry, three fragment hits were identified. These molecules bind the protein at two different regions distant from the usual binding groove highlighting new possibilities for selective modulation of 14-3-3 complexes.

Název v anglickém jazyce

Set-up and screening of a fragment library targeting the 14-3-3 protein interface

Popis výsledku anglicky

Protein-protein interactions (PPIs) are at the core of regulation mechanisms in biological systems and consequently became an attractive target for therapeutic intervention. PPIs involving the adapter protein 14-3-3 are representative examples given the broad range of partner proteins forming a complex with one of its seven human isoforms. Given the challenges represented by the nature of these interactions, fragment-based approaches offer a valid alternative for the development of PPI modulators. After having assembled a fragment set tailored on PPIs' modulation, we started a screening campaign on the sigma isoform of 14-3-3 adapter proteins. Through the use of both mono- and bi-dimensional nuclear magnetic resonance spectroscopy measurements, coupled with differential scanning fluorimetry, three fragment hits were identified. These molecules bind the protein at two different regions distant from the usual binding groove highlighting new possibilities for selective modulation of 14-3-3 complexes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

MedChemComm

ISSN

2040-2503

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

1796-1802

Kód UT WoS článku

000490887100008

EID výsledku v databázi Scopus

2-s2.0-85073786665