Pseudopeptides with aldehyde or vinylsulfone warheads: Synthesis and antiproteasomal activity

Result code in 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>
Alternative codes found
RIV/61989592:15310/21:73610087
Result on the web
<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>

Result language
angličtina
Original language name
Pseudopeptides with aldehyde or vinylsulfone warheads: Synthesis and antiproteasomal activity
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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