Other Compounds of Biochemical Interest

Metal ions have a profound influence on the hydrolysis of acetyl phosphate, Thus, in the magnesium(ii)-catalysed system P—O bond flssion 

Acetate kinase is phosphorylated by acetyl phosphate and it has been shown that the phosphoenzyme can synthesise ATP from ADP, and acetyl phosphate from acetate. The mode of decomposition of carbamyl phosphate in aqueous solution is pH dependent and can proceed with either the production of ammonia and carbon dioxide (equation 1), or cyanate (equation 2). No cyanate could be detected during the hydrolysis 

Interest in presqualene pyrophosphate continues and it is claimed that the structure (88) assigned to a squalene precursor is incorrect. Presqualene pyrophosphate has been shown to contain a cyclopropyl ring (89), and both (89) and its parent alcohol have been synthesised. -Mechanisms for the conversion of (89) into squalene have been pub-lished. - 

The substrate specificity of farnesyl pyrophosphate synthetase has been studied using 3-methyl-2-aIkenyl pyrophosphates (90) as models. When (90) bears a large side-chain i.e. R = C4H9), the reaction with isopentenyl pyrophosphate ceases after the formation of (91) and this reaction has been 

Neopterin cyclic phosphate (92) has been isolated as an intermediate in the biosynthesis of pteridines from GTP in Comamonas Tracer studies show that the phosphoryl group in (92) originates from the 

Prenyl transferase, which catalyses the addition of an allylic pyrophosphate to iso-pentenyl pyrophosphate, also catalyses the hydrolysis of geranyl pyrophosphate.104 Inorganic pyrophosphate stimulates this hydrolysis, and the C—O bond is broken in 

Donella, G. Clari, and V. Moret, Biochim. Biophys. Acta, 1975, 397, 519. 

A rigorous structural proof of the insecticidal exotoxin (34) from Bacillus thurin-giensis has now been published,107 confirming the a-configuration of the glucosidic bond. The total synthesis of (34) is further confirmation of the correctness of the structural assignment.108 The exotoxin inhibits RNA synthesis in insects and animals and affects the incorporation of orotic acid into nuclear RNA.109 

CNDO/2 Theoretical calculations have been used to predict the favoured conformations of creatine and creatine derivatives, including phosphocreatine. These calculations predict that phosphocreatine may adopt conformation (35) to avoid unnecessary steric and electrostatic repulsions.110 The possibility also exists that creatine kinase phosphorylates creatine stereospecifically to form the favoured conformation (35) at the active site of the enzyme. When chicks are fed a diet containing cyclocreatine (l-carboxymethyl-2-iminoimidazole), the phosphorylated 

Prystag, L. Kalvoda, and F. Sorm, Coll. Czech. Chem. Comm., 1975, 40, 1775. 

2-(Dansylamino)ethyl triphosphate (76) is a fluorescent substrate for heavy meromyosin-ATPase, behaving like ATP. Marked increases in the excitation and emission spectra of (76) on addition of heavy meromyosin are observed and the maximum of the emission spectra undergoes a slight 

Further evidence on the structure of presqualene pyrophosphate (78) has been put forward confirming earlier proposals, and the enzymic 

A new microbial metabolite, phosphoramidon (79), has been isolated from a strain of Streptomyces and its structure determined. The 

Umezawa, K. Tatsuta, O. Izawa, and T. Tsuchiya, Tetrahedron Letters, 1972, 97. 

The equilibrium established between methylenetriphenylphosphorane and ethyltriphenylphosphonium bromide in THF has been investigated by quenching with benzaldehyde. 

Hutchinson, in Organophosphorus Chemistry , ed. S. Trippett (Specialist Periodical Reports), The Chemical Society, London, 1977, Vol. 8, p. 133. 

The cyclization of polyolefin terpenes occurs readily once they have been converted into terminal epoxides. The tetracyclic diterpenes 3a- and 3/S-kaurene have been prepared enzymically from chemically synthesized (/ ,5)-14,15-oxidogeranylgeranyl pyrophosphate (42), providing another example of this cyclization. Trimethyl-aluminium can promote the non-enzymic cyclization of the diethyl ester of neryl phosphate (43), presumably a carbonium ion, to 4-t-butyI-l-methylcyclohexene.  

Two pathways are possible for the acid hydrolysis of A -phosphorocreatine (44) to orthophosphate. Both pathways involve metaphosphate as an intermediate, but at pH 1 creatine (45) is the major product, while at pH 1 creatinine (46) is formed as the major product. This observation has led to the prediction that, in the creatine-kinase-catalysed phosphorylation of ADP by (44), metaphosphate 

The majority of newly reported nucleoside 5 -monophosphates have been prepared using phosphorus oxychloride in trialkyl phosphate solution. These include the monophosphates of 2-fluoroadenosine, 2-amino-6-chloro-9-(/S-D-ribofuranosyl)-purine, bredinin (6), cordycepin 2 -azido-2 -deoxyadenosine, 2 -fluoro- 

2 -deoxycytidine, 5-iodoacetamidomethyl- and 5-methoxymethyl-, 5-benzyloxy-methyl-, 5-acetyl-, 5-allyI-, and 5-azidomethyl-2 -deoxyuridine, and several N- 

Among new polyphosphate esters which have been isolated recently are retinol pyrophosphate from rat thyroid and rra j-farnesyl triphosphate from Gibberella fujikuroi. In each case the terminal phosphoryl residue in ATP was incorporated into the polyphosphate, but in neither case has a biological 

A total synthesis of the insecticidal exotoxin (34 R = R = R = H, R = PO3H2) was achieved by the action of phosphorus oxychloride on the protected nucleoside (34 R = PhCO,R = MeCO,R = Me,R = H) hydrolysis of the initial phosphorylation product with sodium hydroxide gave 

A blue fluorescent compound isolated from Photobacterium phosphoreum has been identified as D-er //trn-neopterin-2, 3 -cyclic phosphate (35) by degradation and comparison with the synthetic cyclic phosphate. The latter was obtained by treatment of the 3 -phosphate with DCCD.  

Cyclophosphamide (36 R = H) is an effective agent for the treatment of many animal and human tumours and is oxidized in vivo by a mixed function oxidase of liver microsomes to produce a cytotoxic form of the drug. It was reported earlier that 4-hydroxy-cyclophosphamide (36 R = OH), a product of the oxidation of (36 R = H) with Fenton s reagent, was the 

Sugiura, H. Yamashita, and M. Goto, Bull. Chem. Soc. Japan, 1972, 45, 3564. 

---

Gas chromatography (GC) or gas liquid chromatography (GLC) as a method for analysis of K vitamins is not used as frequently as for other compounds of biochemical interest (e.g., determination of fatty acids). The main reason of this fact can be seen in a possible degradation of the vitamin K molecules on the heated GC-columns. Lefevere et al. [2] and Lambert et al. [17] reviewed early GC methods, where among other things electron capture detection was used for determination of VKl and VK epoxide. 

Limitations of MNDO. From its inception, some important limitations of MNDO were apparent. Sterically crowded molecules were calculated too unstable for example, the AHf of neopentane is predicted by MNDO to be —24.6 kcal/mol, compared with the observed -40.3 kcal/mol. On the other hand, four—membered rings were predicted to be too stable, this reaching a limit in cubane, which was predicted to be 49.6 kcal/mol too stable. Later on, other limitations were discovered, the most important from a biochemical standpoint being the virtually complete lack of a hydrogen bond. Other deficiencies included the extreme instability of hypervalent molecules. This effectivdy precluded the application of MNDO to organophosphorus compounds of biologic interest. Finally, activation barriers were predicted to be too high. 

Of biochemical interest is the presence of quite significant amounts (up to 5%) of the iridoid glycoside loganin (see page 188) in the fruit pulp of Strychnos nux-vomica. This compound is, of course, an intermediate in the biosynthesis of strychnine and other terpenoid indole alkaloids. 

Regular readers of this series of Reports will notice that this Chapter has undergone fission. This is principally due to the ever increasing number of papers on organophosphorus compounds in the chemical and biochemical literature. As a consequence, topics concerning nucleotides and nucleic acids are discussed in Chapter 8 while other topics relating to the reactions of biochemically interesting phosphorus compounds remain in this chapter. 

The primary compounds given above are combined with other substances to form conjugates of biochemical interest. Cysteine is contained in the important tripeptide, glutathione, and is utilized to conjugate with... 

The isotopic exchange of a large number of other organic compounds has been reported, some of which are of biochemical interest. 

ALIS reports only compounds that bind directly to the target of interest, preventing false positives that arise from off-target activity or interactions with substrates or other reagents. Since ALIS directly identifies bound components by MS, the incidence of false positives based on bulk effects and non-specific binding is lower than that of biochemical assays that yield a secondary readout of activity. 

The organoselenium compounds, their chemistry, and methods of preparation are discussed in the literature (3,4,7,11,12,14,59). Selenium-containing polymers are of interest because of their semiconducting and plastic properties. The biologically important compounds include selenoaminocarboxylic acids and derivatives, selenium-containing peptides, and selenium derivatives of pyrimidines, purines, cholines, steroids, coenzyme A, and other compounds (4,14). The biochemical and medical aspects and uses of oiganoselenium compounds have also been discussed (13,14,60—62). 

Professor French was intensely interested in the mechanism of hydrolysis of starch, glycogen, and other polymers of D-glucose by various types of enzymes, and by acids. He was also interested in elucidating the biochemical pathways for the synthesis of these polymers, and in methods for characterization of the compounds, A very clever method for studying the mechanism of an enzyme reaction was introduced in... 

---