Isoxazole-Based Compounds Targeting the Taxane-Binding Site of Tubulin.

Taxanes and other tubulin-targeting medications are essential for treating advanced malignancies, especially in patients undergoing less aggressive chemotherapy. However, their clinical efficacy is often limited by significant off-target toxicity and adverse side effects. In this study, the synthesis and characterisation of novel steroidal A-ring-fused isoxazoles, which were obtained through iodine-mediated oxidative cyclization of dihydrotestosterone (DHT)-derived α,β-unsaturated oximes, are reported.

Phenylacetic acid metabolism in land plants: novel pathways and metabolites.

In recent years, substantial progress has been made in exploring auxin conjugation and metabolism, primarily aiming at indole-3-acetic acid (IAA). However, the metabolic regulation of another key auxin, phenylacetic acid (PAA), remains largely uncharacterized. Here, we provide a comprehensive exploration of PAA metabolism in land plants.

A monomer-dimer switch modulates the activity of plant adenosine kinase.

Adenosine undergoes ATP-dependent phosphorylation catalyzed by adenosine kinase (ADK). In plants, ADK also phosphorylates cytokinin ribosides, transport forms of the hormone. Here, we investigated the substrate preferences, oligomeric states, and structures of ADKs from moss (Physcomitrella patens) and maize (Zea mays) alongside metabolomic and phenotypic analyses.

Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1.

Protein lipidation is a post-translational modification that confers hydrophobicity on protein substrates to control their cellular localization, mediate protein trafficking, and regulate protein function. In particular, protein prenylation is a C-terminal modification on proteins bearing canonical motifs catalyzed by prenyltransferases. Prenylated proteins have been of interest due to their numerous associations with various diseases.

Dihydrotestosterone-based A-ring-fused pyridines: Microwave-assisted synthesis and biological evaluation in prostate cancer cells compared to structurally related quinolines.

Dysfunction of the androgen receptor (AR) signalling axis plays a pivotal role in the development and progression of prostate cancer (PCa). Steroidal and non-steroidal AR antagonists can significantly improve the survival of PCa patients by blocking the action of the endogenous ligand through binding to the hormone receptor and preventing its activation. Herein, we report two synthetic strategies, each utilizing the advantages of microwave irradiation, to modify the A-ring of natural androgen 5α-dihydrotestosterone (DHT) with pyridine scaffolds.

Biochemical and structural basis of polyamine, lysine and ornithine acetylation catalyzed by spermine/spermidine N-acetyl transferase in moss and maize.

Polyamines such as spermidine and spermine are essential regulators of cell growth, differentiation, maintenance of ion balance and abiotic stress tolerance. Their levels are controlled by the spermidine/spermine N -acetyltransferase (SSAT) via acetylation to promote either their degradation or export outside the cell as shown in mammals. Plant genomes contain at least one gene coding for SSAT (also named NATA for N-AcetylTransferase Activity).