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The site-selective incorporation of fluorescent amino acids into proteins has emerged as a valuable alternative to expressible protein reporters. For successful application, a robust and scalable, yet flexible, route to non-natural amino acids is required. This work describes an improved synthesis of coumarin-conjugated lysine derivatives where fluorinated variants are accessed. These analogues can be utilized at low pH and should find application probing biological processes that operate under acidic conditions.
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http://dx.doi.org/10.1021/acs.joc.7b03214 | DOI Listing |
Commun Biol
September 2025
Department of Pharmacology, UT Southwestern Medical Center, Dallas, 75390, TX, USA.
The WNK-OSR1/SPAK protein kinase pathway regulates ion homeostasis and cell volume, but its other functions are not well understood. To discover undefined signaling functions, we utilized experimentally-derived binding specificity to predict interactions and relative affinities with the conserved C-terminal (CCT) domains of OSR1 and SPAK, which bind short linear motifs. The upstream kinases WNKs 1-4 and their relatives, the pseudokinases NRBP1/2, also contain CCT-like domains which have conserved folds and motif binding pockets.
View Article and Find Full Text PDFAnal Chem
September 2025
Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Universitaetsstr. 31, Regensburg 93053, Germany.
The conjugation of proteins to the outer membranes of liposomes is a standard procedure used in bioanalytical and drug delivery approaches. Herein, we describe the development of a liposome-based surrogate assay for the quantification of SARS-CoV-2 neutralizing antibodies. Taking into consideration differences in amino acid sequences within the receptor-binding domain (RBD) of SARS-CoV-2 Spike proteins derived from five selected variants of concern (VoC), we studied the impact of coupling chemistries on physicochemical properties and antigenicity.
View Article and Find Full Text PDFInvest New Drugs
September 2025
Departamento de Química and Institute for Advanced Research in Chemical Science (IAdChem), Facultad de Ciencias, Universidad Autónoma de Madrid, Módulo 13, 28049, Madrid, Spain.
The oncogenic transcription factor MYC drives proliferation, metabolism, and therapy resistance in the majority of human cancers, yet its large, nuclear protein-protein interface has long frustrated direct drug discovery. A pivotal breakthrough was the identification of Tribbles pseudokinase 3 (TRIB3) as a high-affinity scaffold that binds the helix-loop-helix/leucine zipper region of MYC, blocks the E3-ubiquitin-ligase, UBE3B, from tagging critical lysines, and thereby prolongs MYC protein half-life while enhancing MYC-MAX transcriptional output. This review integrates structural, biochemical, and in vivo data to show how genetic deletion or pharmacological eviction of TRIB3 collapses MYC levels, silences its gene program, and suppresses tumor growth in B-cell lymphomas and selected solid tumors.
View Article and Find Full Text PDFTheor Appl Genet
September 2025
College of Horticulture, Shenyang Agricultural University, Shenyang, 110866, People's Republic of China.
Mutations in BrMYB31 were responsible for glossy phenotype, which was verified in two allelic mutants and gene silencing analysis. BrMYB31 regulated wax biosynthesis by modulating BrCER4 expression in Chinese cabbage. Plant cuticular wax plays a crucial role in resisting both biotic and abiotic stresses, but its deficiency is beneficial for improving the commercial properties of certain leafy vegetables.
View Article and Find Full Text PDFLeukemia
September 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Tyrosine kinase inhibitors (TKIs) only partially inhibit the growth of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph B-ALL) cells, and often lead to rapid relapse. Therefore, it is essential to elucidate the mechanisms of resistance and develop novel treatment strategies. Histone deacetylases (HDACs) are often dysregulated in hematological malignancies, and many HDAC inhibitors have shown potent antitumor activities.
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