Mersalyl

Other organic mercurials similar in chemical stmcture to chlormerodrin are meraHuride/7(94-2(9-j5y, mercaptomerin/2 (922J-< 4-/7, and mersalyl [486-67-9]. Mercury-based diuretics (qv) are no longer in use. 

Mersalyl sodium (SALYRGAN) 1-2 ml of 100 mg/ml solution IM twice weekly... 

Certain foreign compounds may cause the retention or excretion of water. Some compounds, such as the drug furosemide, are used therapeutically as diuretics. Other compounds causing diuresis are ethanol, caffeine, and certain mercury compounds such as mersalyl. Diuresis can be the result of a direct effect on the kidney, as with mercury compounds, which inhibit the reabsorption of chloride, whereas other diuretics such as ethanol influence the production of antidiuretic hormone by the pituitary. Changes in electrolyte balance may occur as a result of excessive excretion of an anion or cation. For example, salicylate-induced alkalosis leads to excretion of Na+, and ethylene glycol causes the depletion of calcium, excreted as calcium oxalate. 

Table 7.3. Effects of various inhibitors on [a32P]ADP uptake into E. coli cells expressing several adenine nucleotide carriers. E. coli cells were preincubated for 10 min with lysozyme (2.5 mg/ml) to allow penetration of the reagents across the outer membrane. The inhibitors used were bongkrekic acid (BKA, 50 pM), carboxyatractyloside (CAT, 1 mM), N-elhylmaleimide (NEM, 1 mM), pyridoxal 5 -phosphate (PLP, 2 mM), and mersalyl (100 pM). [a32P]ADP uptake by AAC2(A.t.), AACKN.sp.), HMP31(Tg.), and ANTI (H.h.) was measured at a substrate concentration of 10, 100, 50, and 200 pM, respectively (Voncken et al. 2002 Tjaden et al. 2004 Leroch et al. 2005 Leroch 2006)...

Lovenberg, Buchanan, and Rabinowitz (65) tested the response of ferredoxin to mercury compounds. Two mercurial reagents used, p-mer-curibenzoate (PCMB) and o-((3-hydroxymercuri-2-methoxypropyl)car-bamyl)phenoxyacetate (sodium mersalyl) reacted rapidly with ferredoxin and caused a bleaching of the visible spectrum and a concomitant loss of biological activity. C. pasteurianum ferredoxin was titrated with PCMB as described by Boyer (24) and the results showed that 20 moles of PCMB reacted with 1 mole of ferredoxin. In another determination, 2 moles of PCMB reacted with 1 mole of sodium sulfide. Since ferredoxin contained 7 moles of inorganic sulfide and 8 moles of half-cystine residues, 22 (7 x 2 = 14 14 + 8 = 22) moles of PCMB would be expected to react with 1 mole of ferredoxin. These data, summarized in Table 8, are consistent with the existence of two types of sulfur in ferredoxin. This conclusion was supported by the presence of half-cystine residues in ferredoxin after inorganic sulfide had been removed by acid hydrolysis, as well as results of sulfur analyses, which showed an amount of sulfur greater than could be attributed to half-cystine residues. 

Fig. 6. Absorption spectra of native ferredoxin, mersalyl-ferredoxin, and apoferredoxin. (Lovenberg, Buchanan, and Rabinowitz (65)).

Melarsoprol [me LAR soe prole] is a derivative of mersalyl oxide, a trivalent arsenical. 

The influence of mercurials on the NADPH-cytochrome c reductase activity is complex. The activity in microsomes is stimulated about 50% by p-mercuribenzoate (11). Mersalyl inhibits the NADPH-cytochrome c reductase activity (S87). 

Fia. 8. Absorption spectrum of the soluble iron-sulfur protein (4 mg/ml) isolated from complex I. Dashed line, after treatment with dithionite dotted line, after treatment with sodium mersalyl to destroy the iron-sulfur chromophore. From Hatefi et al. (Si),... 

Fia. 9. Spectral characteristics of the soluble NADH dehydrogenase (1.6 mg/ml) isolated from complex I. Traces 1, spectrum of oxidised enzyme 2, NADH-reduced enzyme 5, dithionite-reduced enzyme 4, flavin contribution to 1 after destruction of iron-sulfur chromophore with sodium mersalyl 3, iron-sulfur contribution to l obtained by subtraction of 4 from 1 6, 4 plus dithionite showing that after destruction of the iron-sulfur chromophore with mersalyl and reduction of flavin with dithionite the enzyme has no absorption in the visible region. From Hatefl and Stempel (40). 

Fia. 27. Absorption spectra of succinate dehydrogenase (A), its larger subunit (B), and its smaller subunit (C). (A) Trace 1, oxidized succinate dehydrogenase trace 2, flavin contribution to the spectrum of oxidized enzyme trace 5, iron-sulfur contribution to the spectrum of oxidized enzyme trace 4, oxidized enzyme treated with dithionite trace 3, oxidized enzyme treated with sodium mersalyl and dithio-nite. Protein = 1.48 mg/ml. (B) Trace 1, oxidized trace 2, flavin contribution to trace 1 trace 3, after treatment of 1 with sodium mersalyl and dithionite. Protein = 3.0 mg/ml. (C) Trace 1, oxidized trace 2, after treatment with mersalyl trace 3, after treatment of 2 with dithionite. Protein = OA mg/ml. From Davis and Hatefi U43). 

Folic Acid 460.6 Fluocortolone Pivalate 483.9 Mersalyl Acid... 

In mitochondrial research the phosphate-transporting protein from rat liver mitochondria has been labeled with ° Hg-mersalyl At For protein labeling with astatine (alpha emitter) the following procedures may be u reaction of the protein with p-astatobenzoic acid < ndensation reaction with peptide bond and protein acetylation While labeling by the above procedures seems to be sufficiently stable a remarkable instability of the At-label was obserwd when astatinated protein was prepared electrophoretically 202) jjjg results of these authors indicate that the tyrosine-astatine bond is unstable. The conclusion of Vau an et al. that astatinated proteins lore as much as 50% of their biological activity and, in addition, are extremely toxic, is very serious. 

Fig. 10.5. Notable examples of Rcelp inhibitors. Abbreviations shown refer to At,-tosyl-l-phenylalanine chloromethyl ketone (TPCK), p-hydroxymercnribenzoic acid (pHMB), p-hydroxymercuriphenylsulfonic acid (pHMS), mersalyl acid (MSA), (acyloxy)methyl ketone (AOMK), and National Service Center (NSC).

The LC/AAS has been employed for many years and Holak [43] used it to monitor the separation of a number of mercury containing drugs, mersalyl, thimerosal and phenyl mercuric borate. Suzuli et al. [44] used the technique to identify the heavy metals bound to isoproteins extracted from liver tissue. Robinson and Boothe [45] used the selectivity of the LC/AA system to monitor the alkyl lead compounds in sea water and Messman and Rains [46] separated four alkyl leads. 

Singer et al. [305] characterised five different thiol groups in the Site 1 segment of the respiratory chain on the basis of different reactivity towards thiol reagents (see also Ref. 306). An interesting finding is that the reaction of mersalyl halves the apparent number of binding sites of rotenone or piericidin [306]. 

A number of workers have been able to isolate a protein, covalently linked to radioactive Af-ethylmaleimide, identified as the mitochondrial phosphate transporter [122,193-196]. The isolation and identification of the transporter was based for the most part on the maleimide and mersalyl reactivity of the protein. The molecular weight of the protein isolated from different sources varies from 27000 to 34000. Because of the covalent linkage to the irreversible inhibitor, reconstitution of transport was not feasible. 

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