Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00499970" target="_blank" >RIV/61388963:_____/18:00499970 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389013:_____/18:00499970 RIV/00216208:11310/18:10389650

Výsledek na webu

<a href="http://dx.doi.org/10.1021/acschembio.8b00791" target="_blank" >http://dx.doi.org/10.1021/acschembio.8b00791</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschembio.8b00791" target="_blank" >10.1021/acschembio.8b00791</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes

Popis výsledku v původním jazyce

Identifying protein targets of bioactive small molecules often requires complex, lengthy development of affinity probes. We present a method for stochastic modification of small molecules of interest with a photo-activatable phenyldiazirine linker. The resulting isomeric mixture is conjugated to a hydrophilic copolymer decorated with biotin and a fluorophore. We validated this approach using known inhibitors of several medicinally relevant enzymes. At least a portion of the stochastic derivatives retained their binding to the target, enabling target visualization, isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach an thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized probe.

Název v anglickém jazyce

Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes

Popis výsledku anglicky

Identifying protein targets of bioactive small molecules often requires complex, lengthy development of affinity probes. We present a method for stochastic modification of small molecules of interest with a photo-activatable phenyldiazirine linker. The resulting isomeric mixture is conjugated to a hydrophilic copolymer decorated with biotin and a fluorophore. We validated this approach using known inhibitors of several medicinally relevant enzymes. At least a portion of the stochastic derivatives retained their binding to the target, enabling target visualization, isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach an thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized probe.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

ACS Chemical Biology

ISSN

1554-8929

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

3333-3342

Kód UT WoS článku

000454568000015

EID výsledku v databázi Scopus

2-s2.0-85058505988