A5046896240- Plant nutrient uptake and metabolism
- Phytase and its Applications
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Fungal and yeast genetics research
- Trace Elements in Health
- Iron Metabolism and Disorders
- Advanced biosensing and bioanalysis techniques
- Microfluidic and Capillary Electrophoresis Applications
- Pancreatic function and diabetes
- Antimicrobial Peptides and Activities
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Cyclization and Aryne Chemistry
- Amino Acid Enzymes and Metabolism
- Analytical Chemistry and Chromatography
- Bacteriophages and microbial interactions
- Plant Stress Responses and Tolerance
- Parathyroid Disorders and Treatments
- Folate and B Vitamins Research
- Photosynthetic Processes and Mechanisms
- Metabolism and Genetic Disorders
- Genetic and Kidney Cyst Diseases
- Carbohydrate Chemistry and Synthesis
- Origins and Evolution of Life
University of Freiburg
2019-2024
Shanghai Institute of Organic Chemistry
2015-2023
Chinese Academy of Sciences
2015-2023
University of Lausanne
2023
China Datang Corporation (China)
2015
Abstract The analysis of myo -inositol phosphates (InsPs) and pyrophosphates (PP-InsPs) is a daunting challenge due to the large number possible isomers, absence chromophore, high charge density, low abundance, instability esters anhydrides. Given their importance in biology, an analytical approach follow understand this complex signaling hub desirable. Here, capillary electrophoresis (CE) coupled electrospray ionization mass spectrometry (ESI-MS) implemented analyze mixtures InsPs PP-InsPs...
In plants, phosphate (P
Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, identified an inositol pyrophosphatase encoded by OCA5 that could regulate and respiration adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels expression of genes involved respiration, representing global mechanism sense ATP central carbon...
Technical challenges have to date prevented a complete profiling of the levels myo-inositol phosphates (InsPs) and pyrophosphates (PP-InsPs) in mammalian tissues. Here, we deployed capillary electrophoresis mass spectrometry identify record InsPs PP-InsPs several tissues obtained from wild type mice newly created PPIP5K2 knockout strain. We observe that mouse colon harbours unusually high PP-InsPs. Additionally, PP-InsP profile is considerably more complex than previously reported for animal...
Eukaryotic cells control inorganic phosphate to balance its role as essential macronutrient with negative bioenergetic impact on reactions liberating phosphate. Phosphate homeostasis depends the conserved INPHORS signaling pathway that utilizes inositol pyrophosphates and SPX receptor domains. Since synthesize various domains bind them promiscuously, it is unclear whether a specific pyrophosphate regulates in vivo, or multiple act pool. In contrast previous models, which postulated...
Nature chose phosphates to activate amino acids, where reactive intermediates and complex machinery drive the construction of polyamides. Outside biology, pathways mechanisms that allow spontaneous selective peptide elongation in aqueous abiotic systems remain unclear. Herein we work uncover those by following chemistry aminoacyl phosphate esters, synthetic counterparts adenylates. The esters act as solubility tags, making hydrophobic acids their oligomers soluble water enabling different...
Eukaryotic cells control inorganic phosphate to balance its role as essential macronutrient with negative bioenergetic impact on reactions liberating phosphate. Phosphate homeostasis depends the conserved INPHORS signaling pathway that utilizes inositol pyrophosphates and SPX receptor domains. Since synthesize various domains bind them promiscuously, it is unclear whether a specific pyrophosphate regulates in vivo, or multiple act pool. In contrast previous models, which postulated...
Significance Statement Kidneys are gatekeepers of systemic inorganic phosphate balance because they control urinary excretion. In yeast and plants, inositol hexakisphosphate kinases (IP6Ks) central to regulate metabolism, whereas their role in mammalian homeostasis is mostly unknown. We demonstrate a renal cell line mice that Ip6k1 Ip6k2 critical for normal expression function the major Na + /Pi transporters NaPi-IIa NaPi-IIc. Moreover, Ip6k1/2 −/− also show symptoms more generalized kidney...
The combinatorial phosphorylation of myo-inositol results in the generation different inositol phosphates (InsPs), which phytic acid (InsP6) is most abundant species eukaryotes. InsP6 also an important precursor higher phosphorylated pyrophosphates (PP-InsPs), such as InsP7 and InsP8, are characterized by a diphosphate moiety ubiquitously found eukaryotic cells. While PP-InsPs regulate various cellular processes animals yeast, their biosynthesis functions plants has remained largely elusive...
Inositol phosphates (InsPs) are ubiquitous in all eukaryotes. However, since there 63 possible different phosphate ester isomers, the analysis of InsPs is challenging. In particular, InsP1, InsP2, and InsP3 already amass 41 which some occur as enantiomers. Profiling these "lower" inositol mammalian tissues requires powerful analytical methods reference compounds. Here, we report an InsP2 with capillary electrophoresis coupled to electrospray ionization mass spectrometry (CE-ESI-MS). Using...
Phosphoramidite analogues of modified cyclotriphosphates provide a general and step-economical synthesis nucleoside triphosphates on scale without the need for protecting groups. These reagents enable rapid access to pure oligophosphates range other that were previously difficult obtain (e.g., NH, CH2, CCl2, CF2 replacements O, phosphono- phosphoimidazolides, -morpholidates, -azidates, -fluoridates). DFT calculations demonstrate selectivity cyclotriphosphate opening reactions proceeds via an...
Abstract Condensed phosphates may exist as linear, cyclic or branched structures. Due to their important role in nature, linear polyphosphates have been well studied. In contrast, (ultraphosphates) remain largely uncharacterised, because they were already described 1950 exceedingly unstable the presence of water, epitomized antibranching-rule. This rule lacks experimental backup, since, best our knowledge, no rational synthesis defined ultraphosphates is known. Consequently, detailed studies...
Cells must strike a delicate balance between the high demand of inorganic phosphate (P i ) for synthesizing nucleic acids and phospholipids its detrimental bioenergetic effects by reducing free energy nucleotide hydrolysis. The latter may stall metabolism.
The water-soluble inositol phosphates (InsPs) represent a functionally diverse group of small-molecule messengers involved in myriad cellular processes. Despite their centrality, our understanding human InsP metabolism is incomplete because the available analytical toolset to characterize and quantify InsPs complex samples limited. Here, we have synthesized applied symmetrically unsymmetrically 13C-labeled myo-inositol phosphates. These probes were utilized combination with nuclear magnetic...
Inositol pyrophosphates (PP-InsPs) are an important group of intracellular signaling molecules. Derived from inositol phosphates (InsPs), these molecules feature the presence at least one energetic pyrophosphate moiety on myo-inositol ring. They exist ubiquitously in eukaryotes and operate as metabolic messengers surveying phosphate homeostasis, insulin sensitivity, cellular energy charge. Owing to absence a chromophore metabolites, very high charge density, low abundance, their analysis...
Magic Spot Nucleotides (MSN) regulate the stringent response, a highly conserved bacterial stress adaptation mechanism, enabling survival under adverse external challenges. In times of antibiotic crisis, detailed understanding response is essential, as potentially new targets for pharmacological intervention could be identified. this study, we delineate MSN interactome in Escherichia coli and Salmonella typhimurium applying family trifunctional photoaffinity capture compounds. We introduce...
A hydrophilic monolithic CEC column was prepared by thermal copolymerization of zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine (MPC), pentaerythritol triacrylate (PETA), either methacrylatoethyl trimethyl ammonium chloride (META) or sodium 2-methylpropene-1-sulfonate (MPS) in a polar binary porogen consisting methanol and THF. typical interaction LC retention mechanism observed for low-molecular weight compounds including amides, nucleotides, nucleosides the separation mode...
The complex phosphorylation pattern of natural and modified pentaphosphorylated magic spot nucleotides is generated in a highly efficient way. A cyclic pyrophosphoryl phosphoramidite (cPyPA) reagent used to introduce four phosphates on nucleosides regioselectively one-flask key transformation. obtained are develop capillary electrophoresis UV detection method, enabling nucleotide assignment bacterial extracts.
Initial studies on the inositol phosphates metabolism were enabled by social amoeba Dictyostelium discoideum. The abundant amount of hexakisphosphate (IP6 also known as Phytic acid) present in allowed discovery more polar pyrophosphates, IP7 and IP8, possessing one or two high energy phosphoanhydride bonds, respectively. Considering contemporary growing interest it is surprising that recent years D. discoideum, has contributed little to our understanding their function. This work fulfils...
Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With cyclic array phosphate esters and diphosphate groups around myo-inositol, these molecular messengers possess the highest charge density found nature. Recent work deciphering inositol pyrophosphate biosynthesis Arabidopsis revealed important functions nutrient sensing, hormone signaling, plant immunity. However, despite rapid...
Inositol pyrophosphates (PP-InsPs) are energetic signaling molecules with important functions in mammals. As their biosynthesis depends on ATP concentration, PP-InsPs tightly connected to cellular energy homeostasis. Consequently, an increasing number of studies involve metabolic disorders, such as type 2 diabetes, aspects tumorigenesis, and hyperphosphatemia. Research conducted yeast suggests that the PP-InsP pathway is activated response reactive oxygen species (ROS). However, precise...
Antibody–drug conjugates (ADCs), integrating high specificity of antigen-targeting antibodies and potency cell-killing chemical drugs, have become one the most rapidly expanding therapeutic biologics in oncology. Although ADCs were widely studied from multiple aspects, overall structural elucidation with comprehensive understanding variants is scarcely reported. Here, for first time, we present a holistic in-depth characterization an interchain cysteine-conjugated ADC, focusing on...
Condensed phosphates are a critically important class of molecules in biochemistry. Non-natural analogues for various applications, such as single-molecule real-time DNA sequencing. Often, contain more than three phosphate units their oligophosphate chain. Consequently, investigations into reactivity enabling new ways functionalization and oligophosphorylation essential. Here, we scrutinize the potential to act arynophiles, paving way follow-up reactions. The aryne reaction is powerful tool...
The pathways and mechanisms that allow spontaneous selective peptide elongation in aqueous abiotic systems remain unclear. Herein we work to uncover those by following the chemistry of aminoacyl phosphates, synthetic counterpart adenylates. Thus, oligomers up dodecamers were synthesized one flask on minute time scale, where consecutive additions activated autonomous phase changes. resulting phases arose from high polar reactive nature which can be dissolved water concentrations 300 mM. Upon...