Reaction with nucleotides

Ring-opened adducts of carboplatin can form not only from reactions with nucleotides, but also by the attack of sulfur amino acids [44]. Reactions with thioether ligands are much more rapid compared with thiols. Surprisingly very stable ring-opened species such as [Pt(CBDCA-0)(NH3)2(L-HMet-S)] are formed, which has a half-life for Met-S,N closure of 28 h at 310 K. Such an intermediate could also play a role in the biological activity of this drug. 

Reactions with nucleotides have also been carried out in ionic liquids. In this context, the transesterification of iV-acetyl-L-phenylalanine ethyl ester with n-propanol catalysed by subtilisin (previously precipitated and rinsed with n-propanol) was succesfully carried out in [bmim+][PFg ] and [bmim+][BF ] (Fig. 7.4) [23]. 

Reactions with nucleotides proceed via aquation of [(ri -arene)Ru(en)Cl], followed by rapid binding to the 5 -phosphate group, and then rearrangement to give N7, N1 or N3-bound products [83], In competitive reactions of [(q -bi-phenyl)Ru(en)Cl] with 5 -GMP, 5 -AMP, 5 -CMP and 5 -TM P the only final adduct is [(q -biphenyl)Ru(en)(N7-GMP)]. The aqua adducts appear to be more reactive than hydroxo adducts. Hence knowledge of the pJQ values of aqua adducts could be useful in drug design. 

In many cases, optimized reaction buffers, nucleotides, and enzymes are packaged in kits along with detailed protocols by the manufacturers. Beyond the information provided by reagent manufacturers, laboratories need a coUection of experimental protocols (5,6). One such coUection is distributed on a subscription basis and updated quarterly (5). 

A popular alternative to the step utili2ing chromogen is to substitute -hydroxyben2enesulfonate for phenol in the reaction with the pyridine nucleotide ... 

Introduction of the cobalt atom into the corrin ring is preceeded by conversion of hydrogenobyrinic acid to the diamide (34). The resultant cobalt(II) complex (35) is reduced to the cobalt(I) complex (36) prior to adenosylation to adenosylcobyrinic acid i7,i -diamide (37). Four of the six remaining carboxyhc acids are converted to primary amides (adenosylcobyric acid) (38) and the other amidated with (R)-l-amino-2-propanol to provide adenosylcobinamide (39). Completion of the nucleotide loop involves conversion to the monophosphate followed by reaction with guanosyl triphosphate to give diphosphate (40). Reaction with a-ribazole 5 -phosphate, derived biosyntheticaHy in several steps from riboflavin, and dephosphorylation completes the synthesis. 

Ph2CHC02-2-tetrahydrofuranyl, 1% TsOH, CCI4, 20°, 30 min, 90-99% yield. The authors report that formation of the THF ether by reaction with 2-chlorotetrahydrofuran avoids a laborious proce ure that is required when dihydrofuran is used. In addition, the use of dihydrofuran to protect the 2 -OH of a nucleotide gives low yields (24-42%)." The tetrahydrofuranyl ester is reported to be a readily available, stable solid. A tetrahydrofuranyl ether can be cleaved in the presence of a THP ether. ... 

One of the reactions used in determining the sequence ot nucleotides in a strand of DNA is reaction with hydrazine. Propose a mechanism for the following reaction, which occurs by an initial conjugate addition followed by internal amide formation. 

Ojika, M., Wakamatsu, K., Niwa, H. and Yamada, K. 1987. Ptaquiloside, a potent carciogen isolated from bracken fern, Pteridium aquilinum var. latiusculum. structure elucidation based on chemical and spectral evidence, and reactions with aminoacids, nucleotides and nucleosides. Tetrahedron 43 5261-5274. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

The following diphosphates and triphosphates can be prepared by reaction of nucleotide azolides with nucleotides, sugar phosphates, phosphopeptides, or aminohexyl phosphates, a) NAD-analogues and P1, / -dinucleoside-S -diphosphates 801... 

The polymerisation of HCN plus reactions with NH3 and H20 gives the nucleotide bases in cells (Figure 4.4). These reactions are followed by condensation with sugars and phosphate. We assume HCN was present. 

In contrast to the reactivity of N-sulfonyloxy and N-acetoxy esters of arylamides and arylamines, the relative reactivity of protonated N-hydroxy arylamines with nucleophiles generally decreases in the order DNA > denatured DNA > rRNA = protein > tRNA nucleotides s nucleosides s methionine = GSH (2,13-17,30,36,40,127,129, 130). Furthermore, the rate of reaction with DNA was found to be not only first order with respect to N-hydroxy arylamine concentration, but also first order with respect to DNA concentration (127,129,131). These data suggested that the reaction mechanism was... 

In earlier studies [5,6] superoxide detection in mitochondria was equated to hydrogen peroxide formation. However, while it is quite possible that superoxide is a stoichiometric precursor of mitochondrial hydrogen peroxide, it is understandable that the level of hydrogen peroxide may be decreased due to the reactions with various mitochondrial oxidants. Moreover, superoxide level can be underestimated due to the reaction with mitochondrial MnSOD. Several authors [7,8] assumed that mitochondrial superoxide production may be estimated through cyanide-resistant respiration, which supposedly characterizes univalent dioxygen reduction. This method was applied for the measurement of superoxide production under in vitro normoxic and hyperoxic conditions, in spite of the finding [7] that cyanide-resistant respiration reflects also the oxidation of various substrates (lipids, amino acids, and nucleotides). Earlier,... 

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