Phosphate and pyrophosphate groups play a central role in cellular signalling and consequently are of great interest to both medicinal chemists and chemical biologists. However, the design of molecules that can interfere with phosphate-based processes is recognised as a significant challenge, especially when the resulting compounds must show good cellular penetration and stability. Herein, we have reviewed the full range of phosphate bioisosteres currently reported and provided the context of their deployment. We aim to provide a useful reference for medicinal chemists and chemical biologists who are engaged in the design of molecules that target phosphate-binding proteins.

While bacteria have been primarily studied for phosphorus (P) removal in wastewater treatment, fungi and their ability to accumulate intracellular polyphosphate are less investigated. P-accumulating fungal strains were screened from soybean plants and surrounding soil by flask cultivation with potato dextrose broth and KH2PO4 in this study. Mucor circinelloides was selected for its high efficiency in P removal efficiency and high cellular P content. Neisser staining and growth-curve analysis confirmed that M. circinelloides stored polyphosphate intracellularly by luxury phosphate uptake. The effect of culture medium compositions on P removal efficiency and cellular P content was also investigated. Monosaccharides (such as glucose and fructose) and organic nitrogen (N, such as urea, and peptone) promoted fungi growth and P accumulation. M. circinelloides also preferred organic phosphates. When glucose, urea, and phytic acid sodium salt were used as the carbon, N, and P source, respectively, the maximum utilization efficiency was 40.1% for P and 7.08% for cellular P content. In addition, the potential of M. circinelloides for P removal from waste streams was investigated. Compared with the non-inoculated control culture, inoculation with M. circinelloides improved the soluble P removal in treating wastewater centrate, screened manure, and digested manure.

BackgroundPrimary Sjogren’s syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown.MethodsThe mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease.ResultsThe bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells.ConclusionOur study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.

The syntheses of four D-myo-inositol 1,4,5-trisphosphate (InsP(3)) derivatives, incorporating phosphate bioisosteres at the 5-position, are reported. The methyl phosphate ester and sulfate derivatives retain InsP(3) receptor (InsP(3)R) agonist activity; the compounds that possess a methylphosphonate or a carboxymethyl moiety are InsP(3)R antagonists.