Enzyme-Responsive Peptide Thioesters for Targeting Golgi Apparatus.
Journal
Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056
Informations de publication
Date de publication:
20 04 2022
20 04 2022
Historique:
pubmed:
12
4
2022
medline:
22
4
2022
entrez:
11
4
2022
Statut:
ppublish
Résumé
The Golgi apparatus (GA) is the hub of intracellular trafficking, but selectively targeting GA remains a challenge. We show an unconventional types of peptide thioesters, consisting of an aminoethyl thioester and acting as substrates of thioesterases, for instantly targeting the GA of cells. The peptide thioesters, above or below their critical micelle concentrations, enter cells mainly via caveolin-mediated endocytosis or macropinocytosis, respectively. After being hydrolyzed by GA-associated thioesterases, the resulting thiopeptides form dimers and accumulate in the GA. After saturating the GA, the thiopeptides are enriched in the endoplasmic reticulum (ER). Their buildup in ER and GA disrupts protein trafficking, thus leading to cell death via multiple pathways. The peptide thioesters target the GA of a wide variety of cells, including human, murine, and
Identifiants
pubmed: 35404599
doi: 10.1021/jacs.2c02238
pmc: PMC9069992
mid: NIHMS1799699
doi:
Substances chimiques
Peptides
0
diphenylalanine
0
Phenylalanine
47E5O17Y3R
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6709-6713Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL158688
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141386
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA142746
Pays : United States
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