Chem(Pro)2: the atlas of chemoproteomic probes labelling human proteins.

Chemoproteomic probes (CPPs) have been widely considered as powerful molecular biological tools that enable the highly efficient discovery of both binding proteins and modes of action for the studied compounds. They have been successfully used to validate targets and identify binders. The design of CPP has been considered extremely challenging, which asks for the generalization using a large number of probe data.

Selenium-catalyzed allylic C-H phosphoramidation of alkenes.

We report herein a synthesis of allylic phosphoramidates from alkenes by selenium-catalyzed allylic C-H derivatization. This method features mild conditions, broad substrate scope, and high functional group tolerance, enabling late-stage modification of a number of complex substrates. In addition, this protocol was applied to modify caryophyllene and produced a photoaffinity probe capable of proteomic target labeling in live HeLa cells.

F NMR enantiodiscrimination and diastereomeric purity determination of amino acids, dipeptides, and amines.

Chiral amino-group compounds are of significance for human health, such as biogenic amino acids (AAs), dipeptides, and even various drugs. Enantiospecific discrimination of these chiral compounds is vital in diagnosing diseases, identifying pathological biomarkers and enhancing pharmaceutical chemistry research. Here, we report a simple and rapid F NMR-based strategy to differentiate chiral AAs, dipeptides, and amines, that were derivatized with ()-2-(2-fluorophenyl)-2-hydroxyacetic acid (()-2FHA).

A Practical Method for Amino Acid Analysis by LC-MS Using Precolumn Derivatization with Urea.

Amino acid (AA) analysis is important in biochemistry, food science, and clinical medicine. However, due to intrinsic limitations, AAs usually require derivatization to improve their separation and determination. Here, we present a liquid chromatography-mass spectrometry (LC-MS) method for the derivatization of AAs using the simple agent urea.

Protein phosphorylation database and prediction tools.

Protein phosphorylation, one of the main protein post-translational modifications, is required for regulating various life activities. Kinases and phosphatases that regulate protein phosphorylation in humans have been targeted to treat various diseases, particularly cancer. High-throughput experimental methods to discover protein phosphosites are laborious and time-consuming.

Prebiotic chemistry: a review of nucleoside phosphorylation and polymerization.

The phosphorylation of nucleosides and their polymerization are crucial issues concerning the origin of life. The question of how these plausible chemical processes took place in the prebiotic Earth is still perplexing, despite several studies that have attempted to explain these prebiotic processes. The purpose of this article is to review these chemical reactions with respect to chemical evolution in the primeval Earth.

In silico approaches uncovering the systematic function of N-phosphorylated proteins in human cells.

Phosphorylation plays a key role in the regulation of protein function. In addition to the extensively studied O-phosphorylation of serine, threonine, and tyrosine, emerging evidence suggests that the non-canonical phosphorylation of histidine, lysine, and arginine termed N-phosphorylation, exists widely in eukaryotes. At present, the study of N-phosphorylation is still in its infancy, and its regulatory role and specific biological functions in mammalian cells are still unknown.

Evaluation of site-diversified, fully functionalized diazirine probes for chemical proteomic applications.

A series of site-diversified, fully functionalized diazirine probes are constructed based on a scaffold shared by several marketed EGFR-targeted drugs. The integrated analysis of protein targets of the site-diversified probe toolkit not only unveils more complete target space and helps suggest false positive targets, but also reveals dynamic events of multi-domain target-ligand interaction.

One-pot synthesis and multiple MS/MS fragmentation studies of phospholysine peptides.

Rationale: Compared with phosphorylation of arginine and histidine, the study of phosphorylation of lysine lags far behind. The major challenges toward the current study of phosphorylation of lysine include synthesis and unambiguous phosphosite identification. This study provided a simple chemical synthesis method to construct phospholysine peptides (pLys peptides) and investigated their fragmentation under multiple activation types.

A sensitive and rapid detection of glutathione based on a fluorescence-enhanced "turn-on" strategy.

Glutathione (GSH) plays important roles in the human body including protecting cells from oxidative damages and maintaining cellular redox homeostasis. Thus, developing a fast and sensitive method for detecting GSH levels in living bodies is of great importance. Many methods have been developed and used for GSH detection, such as high-performance liquid chromatography, capillary electrophoresis, and fluorescence resonance energy-based methods.

Discovery of Novel Pyrazolo[3,4-] Pyridine Derivatives with Dual Activities of Vascular Remodeling Inhibition and Vasodilation for the Treatment of Pulmonary Arterial Hypertension.

Current pulmonary arterial hypertension (PAH) therapeutic strategies mainly focus on vascular relaxation with less emphasis on vascular remodeling, which results in poor prognosis. Hence, dual pathway regulators with vasodilation effect via soluble guanylate cyclase (sGC) stimulation and vascular remodeling regulation effect by AMP-activated protein kinase (AMPK) inhibition provide more advantages and potentialities. Herein, we designed and synthesized a series of novel pyrazolo[3,4-] pyridine derivatives based on sGC stimulator and AMPK inhibitor scaffolds.

A plausible model correlates prebiotic peptide synthesis with the primordial genetic code.

Aminoacyladenylates (5'-aa-AMPs) are key intermediates in peptide synthesis. Here we report analogs of 5'-aa-AMPs, namely nucleotide amidates (aa-N-NMPs), obtained under Hadean conditions. Significantly, dipeptides were detected from the above reactions and their yields varied with different nucleosides through the formation of different aa-N-NMPs.

Development of a stable phosphoarginine analog for producing phosphoarginine antibodies.

Protein phosphorylation is one of the most common and extensively studied post-translational modifications (PTMs). Compared to the O-phosphorylation on Ser, Thr and Tyr residues, our understanding of arginine phosphorylation is relatively limited, both in prokaryotes and eukaryotes, due to the intrinsic instability of phosphoarginine (pArg) and the lack of a feasible method to produce anti-pArg antibodies. We report the design and synthesis of a stable pArg analog, in which the labile N-P bond is replaced with a non-hydrolyzable C-P bond.