Results 211 to 220 of about 279,014 (342)

Covalent drug discovery: Progress against key targets, emerging strategies and lessons learnt

British Journal of Pharmacology, EarlyView.
Abstract Covalent drug discovery is currently experiencing a boom in industrial and academic interest. To date, at least 75 covalent drugs have received regulatory approval, targeting both traditional target classes and more challenging proteins for which other approaches failed. In many cases, unique aspects of covalent targeting are essential for the
Charles P. Brown, Alan Armstrong, David J. Mann   +2 more
wiley   +1 more source

The amino terminal domain of the human α7 nicotinic acetylcholine receptor subunit leads to the functional expression of human/insect receptors

British Journal of Pharmacology, EarlyView.
Human α7 receptors have been characterised in terms of pharmacological properties. Insertion of the N‐terminal domain of the human α7 subunit leads to honeybee and cockroach chimeric receptors activated by ACh and inhibited by α‐Bgt. Insertion of the human cys‐loop leads to cockroach chimeric receptors modulated by PNU.
Alison Cartereau, Chloé Veront, Alexandra Cremades, Priscilla Martin, Remi Gojard, Nicolas Galland, Emiliane Taillebois, Dieudonnée Togbé, Jean‐Yves Le Questel, Steeve H. Thany   +9 more
wiley   +1 more source

LAT1/SLC7A5‐mediated amino acid uptake is regulated by redox signals triggered by formyl‐peptide receptor 2

The FEBS Journal, EarlyView.
FPR2 activation mediates NOX‐dependent LAT1 expression and, in turn, promotes mTORC1 signaling. Upon stimulation with WKYMVm, the FPR2‐NOX2‐ROS axis upregulates LAT1 via increased c‐Myc phosphorylation and decreased miR‐126. Additionally, it promotes CD98 translocation to the plasma membrane.
Myrhiam Cassese, Chiara Brignola, Stefano Marrone, Gabriella Esposito, Rosario Ammendola, Fabio Cattaneo   +5 more
wiley   +1 more source

Enzymatic synthesis of bioactive quinolones and (thio)coumarins by fungal type III polyketide synthases

The FEBS Journal, EarlyView.
Quinolones are valuable scaffolds for drug discovery but are rare in nature. Here, we show that two fungal enzymes, AthePKS and FerePKS, can generate 2‐quinolones and two additional heteroaromatic scaffolds. Using AthePKS, we designed an artificial enzymatic cascade towards an antimicrobial quinolone from a simple precursor and implemented it in E ...
Nika Sokolova, Angelina Osipyan, Lili Zhang, Matthew R. Groves, Sandy Schmidt, Kristina Haslinger   +5 more
wiley   +1 more source

The ALS‐associated E425K mutation uncouples DNAJC7 from the Hsp70 chaperone cycle

The FEBS Journal, EarlyView.
DNAJC7 is a J‐domain protein that plays a key role in protein quality control by regulating Hsp70 activity and preventing protein aggregation. We find that the ALS‐associated E425K mutation in DNAJC7 disrupts productive interaction and activation of Hsp70, thereby blocking the transfer and refolding of client proteins such as TDP‐43.
Bar Elmaleh, Ofrah Faust, Rina Rosenzweig   +2 more
wiley   +1 more source

An update on the landscape of collagen bioactive fragments

The FEBS Journal, EarlyView.
The remodeling of the extracellular matrix releases collagen bioactive fragments, which exert molecular functions and regulate numerous biological processes via several signaling pathways. Here, we summarize the latest findings describing the roles of major bioactive fragments from collagens I, IV, VI, and XVIII in various physiological and ...
Sylvie Ricard‐Blum, Julie Fradette
wiley   +1 more source

Investigating transthyretin variants H88R and I107V in amyloid priming: From destabilization to complete dissociation

The FEBS Journal, EarlyView.
Investigated mutations in transthyretin (TTR) disrupt the F87‐centered hydrophobic core that stabilizes its tetrameric structure. The mild I107V mutation weakens inter‐chain packing, while H88R fully abolishes tetramer formation, yielding a monomeric, aggregation‐prone form. Structural, biophysical, and computational analyses reveal that both mutations
István L. Bódy, Zsolt Fazekas, Nóra Wágner, Anna J. Kiss‐Szemán, Veronika Harmat, Zoltán Pozsonyi, Dóra K. Menyhárd, András Perczel   +7 more
wiley   +1 more source

1H NMR metabolomics and lipidomics analysis of neutrophils reveals biomarkers of ageing, inflammageing and frailty

The FEBS Journal, EarlyView.
Using 1H NMR metabolomics, we measured polar and lipid metabolites from human blood neutrophils from people with frailty (n = 31, mean age 84Y), people with rheumatoid arthritis (n = 16, mean age 55Y), robust older (n = 24, mean age 66Y) and healthy younger people (n = 21, mean age 22Y).
Genna Ali Abdullah, Grace Filbertine, Lucy Gill, Asangaedem Akpan, Marie M. Phelan, Helen Louise Wright   +5 more
wiley   +1 more source

A distinct gene expression mechanism for d‐amino acid utilization in hyperthermophilic archaeon Pyrococcus horikoshii

The FEBS Journal, EarlyView.
The genes PH0137, PH0138, and PH0140 form a cluster in the genome of Pyrococcus horikoshii. The PH0140 gene encodes a transcription factor identified as a d‐amino acid‐responsive regulatory protein (DARP). In feast mode, l‐Ile‐bound DARP binds to the promoter and represses transcription of PH0137 and PH0138. In famine mode, DARP binds to d‐allo‐Ile and
Ryushi Kawakami, Tomoki Kawase, Taira Uehara, Haruhiko Sakuraba, Tomohiko Matsuzawa, Junji Hayashi, Toshihisa Ohshima   +6 more
wiley   +1 more source

Biogenesis of TNF‐α‐insights into proteostasis and inflammation

The FEBS Journal, EarlyView.
TNF‐α biogenesis, trafficking, and signalling are tightly and reciprocally coupled to cellular proteostasis systems, including ER chaperones and endoplasmic reticulum‐associated degradation. This bidirectional crosstalk determines whether TNF‐α responses are adaptive or proteotoxic.
Bailasan Haidar, Céline Philippe, Eric Chevet, Jiří Zahradník   +3 more
wiley   +1 more source