Pseudopeptides with aldehyde or vinylsulfone warheads: Synthesis and antiproteasomal activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F21%3A39917735" target="_blank" >RIV/00216275:25310/21:39917735 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/21:73610087

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045206821006052?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206821006052?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2021.105228" target="_blank" >10.1016/j.bioorg.2021.105228</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pseudopeptides with aldehyde or vinylsulfone warheads: Synthesis and antiproteasomal activity

Popis výsledku v původním jazyce

The comparative study of new proteasome inhibitors based on salicylic acid-modified pseudo-tripeptides terminated with aldehyde or vinylsulfone is presented. We described the synthesis of 11 pairs of pseudopeptides and their properties related to the proteasome inhibition were determined. The effects of integrated amino acids (combinations of leucine, phenylalanine, tryptophan, proline, cyclohexylalanine or norleucine residues) on the activity of the proteasome were investigated. Compounds preferentially inhibited the chymotrypsin 135-subunit of the proteasome in cell-based assays compared with the 131- and 132-subunits, with IC50 values in mid-nanomolar ranges being obtained for the most active members. Our comparative study demonstrated that aldehydes were able to inhibit the proteasome in cells more effectively than vinylsulfones. These results were corroborated by the accumulation of polyubiquitinated proteins in treated cells, GFP accumulation in a reporter cell line and the ability of new compounds to induce apoptotic cell death.

Název v anglickém jazyce

Pseudopeptides with aldehyde or vinylsulfone warheads: Synthesis and antiproteasomal activity

Popis výsledku anglicky

The comparative study of new proteasome inhibitors based on salicylic acid-modified pseudo-tripeptides terminated with aldehyde or vinylsulfone is presented. We described the synthesis of 11 pairs of pseudopeptides and their properties related to the proteasome inhibition were determined. The effects of integrated amino acids (combinations of leucine, phenylalanine, tryptophan, proline, cyclohexylalanine or norleucine residues) on the activity of the proteasome were investigated. Compounds preferentially inhibited the chymotrypsin 135-subunit of the proteasome in cell-based assays compared with the 131- and 132-subunits, with IC50 values in mid-nanomolar ranges being obtained for the most active members. Our comparative study demonstrated that aldehydes were able to inhibit the proteasome in cells more effectively than vinylsulfones. These results were corroborated by the accumulation of polyubiquitinated proteins in treated cells, GFP accumulation in a reporter cell line and the ability of new compounds to induce apoptotic cell death.

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

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

—

Svazek periodika

115

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

105228

Kód UT WoS článku

000704036500008

EID výsledku v databázi Scopus

2-s2.0-85112005871