Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation.

The AMP transferase, FICD, is an emerging drug target finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER resident chaperone BiP/GRP78. Despite increasing evidence linking excessive BiP/GRP78 AMPylation to human diseases, small molecules to inhibit pathogenic FICD variants are lacking.

Synthetic applications of the Cannizzaro reaction.

The Cannizzaro reaction has emerged as a versatile synthetic tool for the construction of functionalized molecules. Dating back to the 19th century, this reaction, though initially used for the synthesis of an alcohol and acid functionality from aldehydes, has henceforth proven useful to generate diverse molecular entities using both intermolecular and intramolecular synthetic strategies. Immense applications in the synthesis of hydroxy acids and esters, heterocycles, fused carbocycles, natural products, and others with broad substrate scope have raised profound interest from methodological and synthetic standpoints.

Clinical advances in analytical profiling of signature lipids: implications for severe non-communicable and neurodegenerative diseases.

Background: Lipids play key roles in numerous biological processes, including energy storage, cell membrane structure, signaling, immune responses, and homeostasis, making lipidomics a vital branch of metabolomics that analyzes and characterizes a wide range of lipid classes. Addressing the complex etiology, age-related risk, progression, inflammation, and research overlap in conditions like Alzheimer's Disease, Parkinson's Disease, Cardiovascular Diseases, and Cancer poses significant challenges in the quest for effective therapeutic targets, improved diagnostic markers, and advanced treatments. Mass spectrometry is an indispensable tool in clinical lipidomics, delivering quantitative and structural lipid data, and its integration with technologies like Liquid Chromatography (LC), Magnetic Resonance Imaging (MRI), and few emerging Matrix-Assisted Laser Desorption Ionization- Imaging Mass Spectrometry (MALDI-IMS) along with its incorporation into Tissue Microarray (TMA) represents current advances.

Deletion of mFICD AMPylase alters cytokine secretion and affects visual short-term learning in vivo.

Fic domain-containing AMP transferases (fic AMPylases) are conserved enzymes that catalyze the covalent transfer of AMP to proteins. This posttranslational modification regulates the function of several proteins, including the ER-resident chaperone Grp78/BiP. Here we introduce a mouse FICD (mFICD) AMPylase knockout mouse model to study fic AMPylase function in vertebrates.

Fic and non-Fic AMPylases: protein AMPylation in metazoans.

Protein AMPylation refers to the covalent attachment of an AMP moiety to the amino acid side chains of target proteins using ATP as nucleotide donor. This process is catalysed by dedicated AMP transferases, called AMPylases. Since this initial discovery, several research groups have identified AMPylation as a critical post-translational modification relevant to normal and pathological cell signalling in both bacteria and metazoans.

Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32.

Heat shock protein 90 (Hsp90) is a eukaryotic chaperone responsible for the folding and functional activation of numerous client proteins, many of which are oncoproteins. Thus, Hsp90 inhibition has been intensely pursued, resulting in the development of many potential Hsp90 inhibitors, not all of which are well-characterized. Hsp90 inhibitors not only abrogate its chaperone functions, but also could help us gain insight into the structure-function relationship of this chaperone.

δ,ε-Unsaturated α,β-diamino acids as building blocks for the asymmetric synthesis of diverse α,β-diamino acids.

A building block approach for the synthesis of α,β-diamino acids is described, which involves the diastereodivergent preparation of two sets of orthogonally protected δ,ε-unsaturated α,β-diamino acids as templates for the preparation of 12 new α,β-diamino acids of biological relevance using simple techniques.