Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Perspectives on tissue-selective insulin derivatives

Insulin is a central regulator of metabolic homoeostasis with diverse, tissue-specific actions across multiple organs. Despite major advances in insulin formulations, current therapies rely on systemic delivery and do not reproduce the physiological distribution of endogenous ins...

Retinoid biology from embryonic patterning to adult tissue homeostasis: metabolism, RAR signaling, disease mechanisms, and clinical translation

Vitamin A gives rise to functionally distinct retinoids that regulate vision, embryonic patterning, and adult tissue homeostasis. The principal endogenous transcriptional ligand, all-trans-retinoic acid (ATRA), activates RARα, RARβ, and RARγ within RAR-RXR heterodimers; this mech...

Transient receptor potential channel activation targets multiple stages of the schistosome parasite

Schistosomiasis, a neglected tropical disease caused by infection with parasitic blood flukes of the genus Schistosoma , affects more than 250 million people worldwide. Currently, patients rely on a single medicine, praziquantel (PZQ), discovered half a century ago. To combat dru...

Self-Assembled Monolayers and Solvent Composition Control the Orientation and Work Function of Pyrene-Based [7]Helicenes

Abstract Self-assembled monolayers (SAMs) and solvent composition critically influence the orientation and electronic properties of functional organic molecules, paving the way for energy conversion and optoelectronic devices. PeakForce quantitative nanomechanics atomic force mic...

The role of autoproteolysis and mitoribosomal proteins in the regulation of the mitochondrial LACTB tumor suppressor

Abstract Tumor suppressors represent one of the first lines of defense against malignant transformation, and their inactivation in cells leads to the onset of tumorigenesis. Cancer cells employ various mechanisms to inactivate cellular tumor suppressors, including epigenetic sile...

Cycloserine inhibits glutamate decarboxylase from Mycobacterium tuberculosis

. Both cycloserine enantiomers break the internal aldimine bond between PLP and the conserved Lys277 residue, forming a previously unrecognised PLP-oxime product and subsequently inhibiting catalysis. Given that PLP-dependent enzymes are promising drug targets, understanding the...

Computational Design and Experimental Validation of Photoactive PARP1 Inhibitors

Abstract Light-activated drugs are a promising way to treat localized diseases for which existing treatments have severe side effects. However, their development is complicated by the set of photophysical and biological properties that must be simultaneously optimized. Here we us...

Immunomodulatory Amacstatins facilitate feeding and Rickettsia parkeri transmission by Amblyomma maculatum ticks

Ticks rely on salivary immunomodulators to sustain prolonged blood feeding and transmit pathogens, yet the protein effectors that mediate these processes remain incompletely defined. Here, we characterize three divergent cysteine protease inhibitors—Amacstatins—from the Gulf Coas...

Rhomboid protease RHBDL2 is a calcium-activated suppressor of EGFR signalling in keratinocytes

Abstract Signalling via the epidermal growth factor receptor (EGFR) is indispensable for morphogenesis and tissue homeostasis. It is activated by extracellular ligands, typically released from transmembrane precursors by proteolysis. Ligand shedding activity is provided by the co...

Outside Back Cover: Cycloazulenylene

Cycloazulenylene exhibits a remarkably narrow HOMO–LUMO gap, intense absorption in the visible range, and a unique tubular packing in the solid state. In Research Article e2204400, Tomáš Slanina, Oliver Dumele, and co-workers strained the nonalternant azulene, known for its anti-...