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At least 1,171 records · Page 65Linked to original sources
PubMed2004

Nanocluster magic.

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Cadmium Compounds↗
PubMed2006

Case histories, magic bullets and the state of drug discovery.

The case histories of five modern drugs are taken as a basis for reflection on the state of drug discovery. Two issues intimately associated with drug research are highlighted: the nature of the intellectual process leading to new discoveries; and the possibility that the principle of selective efficacy, which has guided drug research from its beginnings, might need modification, at least in some areas of pharmacotherapy.

Animals↗
PubMed2001

Occlusal magic..

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Dental Occlusion↗
PubMed2004

The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer.

Beta-transducin repeats-containing proteins (beta-TrCP) serve as the substrate recognition subunits for the SCFbeta-TrCP E3 ubiquitin ligases. These ligases ubiquitinate specifically phosphorylated substrates and play a pivotal role in the regulation of cell division and various signal transduction pathways, which, in turn, are essential for many aspects of tumorigenesis. We review the functions of the SCFbeta-TrCP ligases in the light of their relevance to cell growth, survival and transformation. Mechanisms underlying beta-TrCP regulation and their aberration in human and animal cancer as well as prospective of targeting beta-TrCP as a means of anticancer therapy are also discussed.

Animals↗
PubMed2002

Rigidization, preorientation and electronic decoupling--the 'magic triangle' for the design of highly efficient fluorescent sensors and switches.

One of the key interests in the recent development of fluorescent molecular sensors and switches is the realization of systems that show strong signal changes as a response to the chemical trigger. Aiming at rational probe design, this article compiles and compares different promising strategies to extract those supramolecular and photophysical features that allow the construction of molecular devices suitable for efficient signaling. The examples comprise fluorescence 'OFF'-'ON' as well as 'ON'-'OFF' operative systems and the mechanisms, properties, and limitations of the different design concepts are discussed.

Drug Design↗
PubMed2005

Arginine magic with new counterions up the sleeve.

The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator-membrane and activator-carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene >>fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene approximately coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator-carrier and activator-membrane interactions are discussed as supportive of arene-templated guanidinium-carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.

Arginine↗
PubMed1973

The effect of trimethoprim on macromolecular synthesis in Escherichia coli. Regulation of ribonucleic acid synthesis by 'Magic Spot' nucleotides.

During the inhibition of RC(str), but not RC(rel) mutants of Escherichia coli by trimethoprim the unusual nucleotides MSI (guanosine tetraphosphate, ppGpp) and MSII rapidly accumulated. The production of these nucleotides was not dependent on the addition of nucleotide base supplements to RC(str) cultures before trimethoprim, and the MSI nucleotide concentrations in non-supplemented or purine-supplemented cultures were comparable with the concentrations obtained when the cells were inhibited with l-valine (1g/l). Rifampicin rapidly decreased MSI and MSII nucleotide concentrations in trimethoprim-inhibited cultures to the basal values. Several situations were noted, in which MS nucleotide concentrations in trimethoprim-inhibited RC(str) cells could be drastically lowered without giving rise to an immediate resumption of stable RNA accumulation. If RC(str) mutants were first inhibited with trimethoprim and then given purines 15min later, MS nucleotide concentrations fell rapidly, because of a temporarily enhanced rate of accumulation of stable RNA. However, after a further 5min, RNA accumulation stopped, though MS nucleotide concentrations remained low. Also, if either glycine or methionine were added to trimethoprim-inhibited cultures supplemented with purines, RNA accumulation did not resume, though MS nucleotide concentrations rapidly declined. With both amino acids present, there was both a decline in MS nucleotide concentration and a resumption in stable RNA synthesis. These findings suggest that MSI nucleotide concentrations in trimethoprim-inhibited bacteria are not the sole factors in the control of stable RNA synthesis. It is possible that, during the period when the RC(str) cells contained high concentrations of MS nucleotides, some factor important in the MSI-mediated control of stable RNA synthesis was irreversibly inactivated. However, as antibiotics (e.g. chloramphenicol) both abolished high MS nucleotide concentrations and permitted a rapid resumption of stable RNA accumulation in the same conditions, it is more likely that an additional control mechanism has come into play.

Centrifugation, Density Gradient↗