Reactions of {4-[bis(2-chloroethyl)amino]phenyl}acetic acid (phenylacetic acid mustard) with 2'-deoxyribonucleosides

Phenylacetic acid mustard (PAM; 2), a major metabolite of the anticancer agent chlorambucil (CLB; 1), was allowed to react with 2'-deoxyadenosine (dA), 2'-deoxyguanosine (dG), 2'-deoxycytidine (dC), 2'-deoxy-5-methylcytidine (dMeC), and thymidine (T) at physiological pH (cacodylic acid, 50% base). The reactions were followed by HPLC and analyzed by HPLC/MS and/or (1)H-NMR techniques. Although the predominant reaction observed was hydrolysis of PAM, 2 also reacted with various heteroatoms of the nucleosides to give a series of products: compounds 5-31. PAM (2) was found to be hydrolytically slightly more stable than CLB (1). The principal reaction sites of 2 with dA, dG, and with all pyrimidine nucleosides were N(1), N(7), and N(3), resp. Also, several other adducts were detected and characterized. There was no significant difference in the reactivity of 1 and 2 with dG, dA or T, but the N(3) dC-PAM adduct was deaminated easier than the corresponding CLB derivative. The role of PAM-2'-deoxyribonucleoside adducts on the cytotoxic and mutagenic properties of CLB (1) is discussed.     

Muscle oxygen extraction and perfusion heterogeneity during continuous and intermittent static exercise.

The purpose of this study was to compare the effects of intermittent and continuous static exercise on muscle perfusion, perfusion heterogeneity, and oxygen extraction. Perfusion and oxygen uptake of quadriceps femoris muscle were measured in 10 healthy men by using positron emission tomography and [(15)O]H(2)O and [(15)O]O(2) first during intermittent static exercise [10% of maximal static force (MSF)] and thereafter during continuous static exercise at the same tension-time level (5% static; 5% of MSF). In 4 of these subjects, perfusion was measured during continuous static exercise with 10% of MSF (10% continuous) instead of the second [(15)O]O(2) measurement. Muscle oxygen consumption was similar during intermittent and 5% continuous, but muscle perfusion was significantly higher during 5% continuous. Consequently, muscle oxygen extraction fraction was lower during 5% continuous. Perfusion was also more heterogeneous during 5% continuous. When exercise intensity was doubled during continuous static exercise (from 5% continuous to 10% continuous), muscle perfusion increased markedly. These results suggest that continuous, low-intensity static exercise decreases muscle oxygen extraction and increases muscle perfusion and its heterogeneity compared with intermittent static exercise at the same relative exercise intensity.     

Illumination does not affect the membrane potential or the plasma membrane H+-ATPase activity in Micrasterias

The membrane potential (MP) of the unicellular green alga Micrasterias torreyi was found to be −46 to −47 mV (when cultured in Waris medium). In contrast to plant cells in general, light-dark changes neither affected the potential or the membrane resistance in Micrasterias . In comparison, the freshwater plant Elodea showed a light-induced hyperpolarization due to the activating effect of light on the plasma membrane adenosine triphosphatases (PM ATPases) through a signal from chloroplasts. In Micrasterias , the PM H+-ATPase inhibitors Na-orthovanadate and diethylstilbestrol depolarized the potential, but it remained at the same level in light and dark. On the other hand, fusicoccin, which activates the PM H+-ATPases, hyperpolarized the potential clearly (to −56 mV). 3-(3',4'-dichlorophenyl)-1,1-dimethylurea, which blocks the electron transport chain from photosystem (PS)II to PSI and thereby prevents the possible signal transmission from chloroplasts to the PM, depolarized the MP slightly, but did not affect the (lacking) light changes either. The results indicate the presence of a continuous (low) activity of PM H+-ATPases in Micrasterias , which is not stimulated by light. The lack of rapid light-induced changes in Micrasterias MP may be due to an unusual functioning of giant chloroplasts in the ion metabolism of the Micrasterias cell.     

Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)

Background  

The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin.     

Novel CoA-polyamine conjugates for effective inhibition of spermine/spermidine-N1-acetyltransferase

New mimics of the transition state of spermine/spermidine-N(1)-acetyltransferase reaction were prepared starting from aminooxy analogues of spermidine or spermine and SH-CoA. The activity depended on the structure of polyamine fragment of the conjugate and best of the synthesized compounds were active at micromolar concentrations.     

Convergent syntheses and cytostatic properties of 2-chloro-2′-deoxy-2′-fluoroadenosine and its N-isomer

Glycosylation of trimethylsilylated 2,6-dichloropurine 2 with acetate 1 in anhydrous MeCN was investigated. In the presence of SnCl₄, the reaction was regio- and stereoselective affording N⁷-β-glycoside 3 (86%). The use of TMS-Tfl instead of SnCl₄ afforded a ≈ 9:1 mixture of the N⁹-β- and --glycosides 5 and 6 (90%, combined). The title nucleosides were tested for their cytotoxicity.     

Clone diversity of Eiseniella tetraedra (Oligochaeta: Lumbricidae) along regulated and free‐flowing boreal rivers

We have sampled populations of the parthenogenetic and polyploid earthworm Eiseniella tetraedra along the Ume, Vindel and Sävar Rivers in northern Sweden. The Vindel River is one of the last free‐flowing large rivers in NW Europe, while the Ume River, which flows parallel to it, is harnessed with twenty major dams. Clones were identified on the basis of overall enzyme phenotypes that were detected using starch gel electrophoresis. We found that clone pool diversity is higher along the Vindel River than along the Ume River and the clone pool similarity is, in a similar fashion, higher along the free‐flowing river. Evidently the dams stop effectively clone dispersal along the Ume River. Clone diversity is highest at the river mouth. The small free‐running Sävar River had also high clone diversity at the lower course of the river. Clone turnover between years is high. We found no evidence for parallel adaptation of clones along the two rivers.