N-phosphorylation

N-phosphorylation has been reported for HI and H4, modifying HI at lysine residues (N -phosphoryl lysine) and H4 at a histidine residue (1- or 3-phosphoryl histidine) [109]. The modification is acid-labile and alkali-stable, and is destroyed by acid-extraction procedures used in isolating histones. 

Histone kinases responsible for N-phosphorylation have been isolated from regenerating rat liver [109] and Walker-256 carcinosarcoma cells [110]. One kinase with a pH optimum of 9.5 phosphorylated His-18 and His-75 of H4, while the other with a pH optimum of 6.5 phosphorylated lysine of HI. The enzyme from regenerating rat liver phosphorylated H4 at 1-phosphoryl histidine, while the carcinosarcoma enzyme phosphorylated H4 His at the position 3 [111]. Both kinases were cAMP independent [110]. Matthews and colleagues purified a 32-kDa histidine H4 kinase from yeast, Saccharomyces cerevisiae [112,113]. The enzyme phosphorylated His-75 (1-phosphoryl histidine) in H4. His-18 of H4 and other histidines in other core histones were not phosphorylated by this kinase [112]. Protein phosphatases 1, 2A, and 2C could dephosphorylate His-75 of H4 [114]. Applying a gel kinase approach to detect mammalian H4 histidine kinases, Besant and Attwood detected four activities in the 34-41 kDa range with extracts from porcine thymus [115]. 

In regenerating rat liver only pre-existing H4 was phosphorylated at the peak of DNA synthesis [116,117]. The modification has a half-life of two hours and may be involved in replication of DNA [109,116,117]. The histidine kinases in yeast and Physarum polycephalum nuclear extracts are unable to phosphorylate H4 in 

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The third step is hydrolysis of the N-phosphorylated amidines which is carried out by either acid or alkali depending on the substrate. 

From semiamidals, the correspondmg tnfluoromethyl substituted N-acyl mines [25, 28], 1,3-diambutadienes [27], N-sulfonyl mines [5, 29], N sulfinyl mines [30], and N-phosphoryl mines [31] can be obtamed in high yields on reaction with powerful dehydratmg realms like POC -pyndine or tnfluoroacetic anhydnde-pyndme [2, 5]... 

Takeda A, Saheki S, Shimazu T, Takeuchi N Phosphorylation of the 27-kDa gap junction protein by protein kinase C in vitro and in rat hepatocytes. J Biochem 1989 106 723-727. 

Feuerstein, N. Phosphorylation of numatrin and other nuclear proteins by cdc2 containing CTD kinase cdc2/p58. J. Biol. Chem., 266, 16200-16206 (1991)... 

N-phosphorylated phosphazenes are characterized by P=N-PO-se-quences. N-dialkoxyphosphoryl trialkoxyphosphazenes ("pentaesters"),... 

Esters of N-phosphoryl phosphazenes are usually formed by the Staudinger reaction which requires the handling of the extremely toxic phosphoric acid ester azides (eq. 1). For developing new synthetic... 

Formation of P=N-P-Bridges. A simple reliable synthesis of N-phosphorylated phosphazenes which avoid the handling of the dangerous phosphoryl azides consists in a direct reaction of di- and trialkyl-phosphites and carbon tetrachloride with sodium azide in a single step procedure (eq. 11). The phosphoryl azides formed intermediately instantly react with the trialkylphosphites present. Therefore, their... 

An entirely different example for substances with two different phosphorus atoms in the molecule showing only a single NMR signal are O-silylated N-phosphoryl phosphazenes, X2P(OSiMe )=N-POX2 (X =... 

Conjugation of the nitrogen lone pair with the adjacent phosphoryl or carbonyl function was tested by the 13C NMR parameters of the N-phosphorylated and N-acetylated aniline, as well as of their complexes with Lewis acids. (h ). The inductive and resonance constants for the neutral and charged amide groups were determined using the dual substituent parameter (dsp) approach. ( 5). Results are given in the Table. 

The phosphorylation of potassiopyrrole by the chlorides of phosphorous acid shows [21] that the process is selective and leads to the products from N-phosphorylation. The reaction of 2,4-dimethyl- and 2,3,5-trimethylpyrroles with chlorophosphites makes it possible to obtain mono- and diphosphorylated alkylpyrroles, depending on the ratio of the phosphorylating agent and alkylpyrrole [22, 23]. 

In the case of P(III) acid dichlorides, in which the electrophilicity of the phosphorus atom is increased in comparison with that of monochlorides, a decrease in the selectivity of N-phosphorylation must be expected. In fact, the reactions of indole and 2-methylindole with dichloroamidophosphites, dichlorophosphites, and dichlorophosphines lead to bisindolylphosphonites, bisindolylphosphines, and bisindolylphosphinites 18-20 [11,12]. 

Data on the N-phosphorylated derivatives of pyrrole have been reported [29], and the synthesis of 1-methyl-2-diphenylphosphinyl-3-formylindole dimethylhydrazone 31 and tetrahydroindole derivative 32 has also been mentioned [30] ... 

If amidophosphite esters are used, the formation of C(3)-substitution products with a yield of more than 30% is observed along with N-phosphorylation. The authors explain this by the catalytic effect of the amine hydrochloride impurities. 

The assignment of the last signal was confirmed by an alternative synthesis of N-phosphorylated indoline (99 ppm). 

In reaction with amidophosphites hydroxymethylindole 80a gives the N-phosphorylation (80) and O-phosphorylation (81) products [77], At -5°C compound 80 is formed preferentially (80-85%) if the temperature is raised to 80°C its fraction amounts to 65-70%, while that of the O-phosphorylation product 81 is 30-35%. With a twofold excess of the amidophosphite instead of equimolar amount it is possible to obtain the diphosphorylated derivatives of 3-methylindole (82). All the compounds with a tricoordinated phosphorus atom (80-82) are easily oxidized in air to the corresponding compounds with a tetracoordinated phosphorus atom (83-85) ... 

In the presence of sodium alkoxide an unstable intermediate containing sodium substituent at the nitrogen atom is formed. This is converted into the C-phosphorylated (96) or N-phosphorylated (97) derivative, in the latter case undergoing a thermal rearrangement under the reaction conditions, and this was confirmed experimentally. 

The formation of the products from N-phosphorylation and N-alkylation in a ratio of 6 1 was detected in the reaction of phosphites with N-phosphoryltrifluoroacetylindolylphosphonate [102],... 

The N-phosphorylated derivatives of pyrrolidine 134 [125, 126], 2-methoxymethylpyrrolidine 135 [127], and 2-ethoxycarbonylpyrrolidine 136 [128] are formed during the reaction of the corresponding heterocycles with mono- and dichlorides of phosphoric, phosphonic, thiophosphoric, and thiophosphonic acids ... 

The most reactive in this reaction were N-phosphorylated salts of isoquinoline, which hetarylated indole even at room temperature. Pyridine and particularly quinoline are less reactive. With these heterocycles the reaction took place only in the presence of the more active dialkylphosphinic acid chlorides. The steric effects of the substituents at the phosphorus atom have a definite role. It was found that substituents with smaller molecular mass and less branched substituents made it possible to conduct the reaction under milder conditions and lead to an... 

A synthetic approach to /3-sultams containing a direct bond between a tri- or tetracoordinated phosphorus atom and the nitrogen atom of the 1,2-thiazetidine 1,1-dioxide ring has been realized by direct phosphitylation or phosphorylation at nitrogen. Unfortunately, attempts to synthesize N-phosphorylated /3-sultams by reaction with diethyl phosphorochloridate and diethyl phosphorobromidate, generated in situ from diethyl phosphate and carbon tetrachloride or carbon tetrabromide, failed. However, when the /3-sultam is treated with freshly distilled diethyl phosphorochloridite or tetramethylphosphorodiamidous chloride in the presence of triethylamine, the expected AHliethy I phosphite and iV-phosphorodiamidous /3-sultams 150 are obtained (Equation 10). /3-Sultams unsubstituted... 

The possibilities of N-(dialkylphosphoryl)amino acids for the prebiotic syntheses of peptides and polynucleotides have been studied in a series of papers [24,116-122], However, it must be emphasized that the phosphoryl group does not behave as an amino-activating group, the hydrolysis of which would be coupled to peptide bond formation. Actually, further peptide elongation requires the subsequent hydrolysis of the N-terminal phosphoryl group of the ligated product. In the presence of an amino acid ester, dipeptide esters 16 with an unreacted N-phosphoryl protection are formed, support-... 

Because of their abilities in both peptide and nucleic acid oligomerization, N-phosphoryl amino acids could have played an important role in prebiotic chemistry on condition that a plausible pathway of synthesis of these compounds is made available. 

Zu N-(Phosphoryl)-isothioharnstoffen gelangt man durch Umsetzung von Phos-phinsaure-halogeniden mit Isothioharnstoff-Hydrochloriden in Gegenwart molarer Men-gen Triethylamin825 ... 

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