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Thiol Function (thiol + function)
Selected AbstractsStructure,activity analysis of the potentiation by aminothiols of the chromosome-damaging effect of bleomycin in G0 human lymphocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2001George R. Hoffmann Abstract The radioprotective aminothiols 2-[(aminopropyl)amino] ethanethiol (WR-1065) and cysteamine (CSM) potentiate the induction of chromosomal damage by the radiomimetic compound bleomycin (BLM) in G0 human lymphocytes. To investigate the mechanism of potentiation, we measured the clastogenic activity of BLM in the cytokinesis-block micronucleus assay in the presence and absence of amines, thiols, and aminothiols. The hydroxy analog of WR-1065, 2-(3-aminopropylamino) ethanol (WR-OH), potentiates BLM only slightly, indicating the critical nature of the thiol group. As thiols, WR-1065 and CSM may donate electrons for the activation of Fe+2 -BLM or for the regeneration of Fe+2 -BLM from inactive Fe+3 -BLM. The amines putrescine, spermidine, and spermine all potentiate BLM, but they are weaker potentiators than the aminothiols, and they are effective only at high concentrations. Their activity, like that of WR-OH, is probably a consequence of conformational alteration of DNA. Dithioerythritol (DTE) and 2-mercaptoethanol (2-ME), thiols lacking an amino group, are less effective potentiators of BLM than are the aminothiols. The thiol group of WR-1065 and CSM is therefore essential, but insufficient, for explaining the strong enhancement of BLM activity. The cationic nature of CSM and WR-1065, conferred by the amino groups, evidently concentrates the active thiol function at the site of BLM action on DNA. As expected on this basis, the diamine WR-1065 is a more effective potentiator of BLM than is the monoamine CSM, whereas cysteine and N -acetylcysteine (NAC), which lack a net positive charge, potentiate BLM only weakly. These studies suggest that potentiation of the clastogenic action of BLM by aminothiols can be explained by the combination of a thiol-mediated redox mechanism and an amine-mediated targeting of the thiol function to DNA. Environ. Mol. Mutagen. 37:117,127, 2001 © 2001 Wiley-Liss, Inc. [source] New N6 -substituted 8-alkyl-2-phenylmethylsulfanyl-adenines.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2004Title compounds bearing substituents on C(2), C(6) and C(8) were prepared from a newly synthesized pyrimidine derivative 11. The new pyrimidine 11 was generated from compound 2 through two different synthetic schemes. In one pathway, compound 2 was nitrosated, reduced and alkylated to produce com pounds 9, 10 and 11 respectively (Scheme). In an alternate route using compound 2 as the starting material, a coupling reaction using the diazonium salt derived from p -methylaniline afforded the azo derivative 7, which was subsequently alkylated and reductively cleaved to form compounds 8 and 11 respectively (See Scheme). Compound 11 was annulated to the corresponding hypoxanthine derivatives 12,14; compounds 12 and 13 were chlorinated with phosphorus oxychloride, then reacted with amines to yield compound 17 and 20 respectively. Compounds 21, 22 and 23 were obtained by oxidation of the corresponding sulfide as depicted in Scheme. Alkylation of the thiol function of 1 gave a mixture of 3 and 4. Compound 3 was chlo rinated to 5. Nitration of 5 resulted in electrophilic aromatic substitution of the aryl ring and concomitant oxidation of the sulfide to the sulfoxide, producing 6. [source] Synthesis and Quality Control of Thiol Tagged Compound Libraries for Chemical MicroarraysMOLECULAR INFORMATICS, Issue 11 2006Sabine Maier Abstract A method for the synthesis and quality control of compound collections containing reactive thiol functions was developed. Such libraries form the basis for the construction of chemical microarrays to be used in fragment-based screening. Amino-modified polymer membranes fixed into the wells of microtiter plates were used as the solid phase for the nanomole-scale synthesis of a thiol-tagged small molecule library using a spatial one-compound/one-well strategy. A thiolselective Liquid Chromatography-Mass Spectroscopy (LC-MS) protocol of each compound before attachment to the microarray surface was established, allowing an exact determination of compound purity and concentration. The established synthesis and quality control method is an important prerequisite for an accurate read-out of the array compound,target interaction data, and simplifies the usage of small molecule microarrays for low affinity screening. [source] | ||||||||||