1. New aspects in the pathophysiology of cutaneous melanoma: a review of the role of thioproteins and the effect of nitrosoureas
K U Schallreuter, J M Wood Melanoma Res. 1991 Aug-Sep;1(3):159-67.
The importance of thioproteins, essential to the ribonucleotide reduction pathway, has been demonstrated in human primary and metastatic melanoma tissues. The thioredoxin reductase/thioredoxin and the glutathione reductase/glutathione/glutaredoxin electron transfer pathways represent alternative electron donors for ribonucleotide reductase and regulate the synthesis of deoxyribonucleotides, the substrates for DNA synthesis, in the S phase of the cell cycle. In addition to their important role in DNA synthesis and cell division, these thioproteins provide effective antioxidant defence against oxygen radicals and hydrogen peroxide. In human metastatic melanoma cells and tissues the thioredoxin reductase/thioredoxin system is located both in the cell cytosol and on plasma membranes and is under allosteric regulation by calcium. As a consequence, calcium plays an important role in determining the intracellular redox status, cell division and differentiation. Recently, the intracellular redox conditions have been shown to be important in the reaction of alkylating anti-tumour drugs such as the chloroethylnitrosoureas. In addition to previously established mechanisms, these highly reactive drugs inhibit thioredoxin reductase, glutathione reductase and ribonucleotide reductase by chloroethylation of their respective thiolate active sites. Incorporation of the 14C chloroethyl group in drug sensitive and resistant human metastatic melanoma cell lines depends on the redox status, with resistant cells being more oxic than sensitive cells. Thioredoxin reductase is 500-fold more sensitive than glutathione reductase to the newly developed nitrosourea, Fotemustine (diethyl-1-[3,2 chloroethyl]-3-nitrosoureido ethyl phosphonate). It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)
2. Enhanced Osteogenic Potential of Phosphonated-Siloxane Hydrogel Scaffolds
Michael T Frassica, Sarah K Jones, Jakkrit Suriboot, Ahmad S Arabiyat, Esteban M Ramirez, Robert A Culibrk, Mariah S Hahn, Melissa A Grunlan Biomacromolecules. 2020 Dec 14;21(12):5189-5199.doi: 10.1021/acs.biomac.0c01293.Epub 2020 Nov 2.
In a material-guided approach, instructive scaffolds that leverage potent chemistries may efficiently promote bone regeneration. A siloxane macromer has been previously shown to impart osteoinductivity and bioactivity when included in poly(ethylene glycol) diacrylate (PEG-DA) hydrogel scaffolds. Herein, phosphonated-siloxane macromers were evaluated for enhancing the osteogenic potential of siloxane-containing PEG-DA scaffolds. Two macromers were prepared with different phosphonate pendant group concentrations, poly(diethyl(2-(propylthio)ethyl)phosphonate methylsiloxane) diacrylate (PPMS-DA) and 25%-phosphonated analogue (PPMS-DA 25%). Macroporous, templated scaffolds were prepared by cross-linking these macromers with PEG-DA at varying mol % (15:85, 30:70, and 45:55 PPMS-DA to PEG-DA; 30:70 PPMS-DA 25% to PEG-DA). Other scaffolds were also prepared by combining PEG-DA with PDMS-MA (i.e., no phosphonate) or with vinyl phosphonate (i.e., no siloxane). Scaffold material properties were thoroughly assessed, including pore morphology, hydrophobicity, swelling, modulus, and bioactivity. Scaffolds were cultured with human bone marrow-derived mesenchymal stem cells (normal media) and calcium deposition and protein expression were assessed at 14 and 28 days.
3. Supramolecular architecture in azaheterocyclic phosphonates. III. Structures of an ethyl phosphonamidate and an ethyl phosphonate
Anna Pietrzak, Jakub Modranka, Jakub Wojciechowski, Tomasz Janecki, Wojciech M Wolf Acta Crystallogr C Struct Chem. 2018 Aug 1;74(Pt 8):907-916.doi: 10.1107/S2053229618009609.Epub 2018 Jul 13.
The novel crystal structures of ethyl (S)-P-(4-oxo-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-3-yl)-N-[(R)-1-phenylethyl]phosphonamidate, C20H20N3O3PS, I, and diethyl (4-isopropyl-2-oxo-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidin-3-yl)phosphonate, C18H25N2O4PS, II, were characterized by X-ray diffraction analysis. The crystal packing of I is dominated by two infinite stacks composed of symmetry-independent molecules linked by distinctively different hydrogen-bond systems. The structure of II shows a ladder packing topology similar to those observed in related phosphorylated azaheterocycles. Structural studies are supplemented by calculations on the interactions stabilizing the molecular assemblies using the PIXEL method. Additionally, fingerprint plots derived from the Hirshfeld surfaces were generated for each structure to characterize the crystal packing arrangements in detail. The aromaticities of the heterocyclic moieties have been investigated using HOMA and HOMHED parametrization and compared with structures reported previously.
