A new 4D-QSAR approach has been considered. For all investigated molecules the 3D structural models have been created and the set of conformers (fourth dimension) have been used. Each conformer is represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). The investigation of influence of molecular structure of macrocyclic pyridinophanes, t...

Spermine penetrates the mitochondrial matrix at significant rates which increase sharply and non-ohmically with membrane potential. In this respect, spermine uptake is qualitatively similar to that of other cations whose electrophoretic transport has been studied in mitochondria. At 200 mV and 1 mM spermine, the observed rate of spermine uptake was about 7 nmol x mg-1 x min-1, and the rate cons...

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of s...

Polyamine levels are elevated in the organs and tissues of cancer patients due to increased synthesis and active intercellular transport in cancer cells. Because increased polyamine levels are associated with poor prognosis, the effect of polyamines on the malignant potential of cancer cells was investigated. Highly metastatic colon cancer cells (HT-29) were cultured under either normoxia (21% ...

Polyamines are known to be essential for normal cell growth and differentiation. However, despite numerous studies, specific cellular functions of polyamines in general and individual polyamines in particular have remained only tentative, because of a lack of appropriate cell lines in which genes of polyamine-synthesizing enzymes have been disrupted by gene targeting. With the use of homologous...

We have evaluated the possible role of proteoglycans in the uptake of spermine by human lung fibroblasts. Exogenous glycosaminoglycans behaved as competitive inhibitors of spermine uptake, the most efficient being heparan sulphate (Ki=0.16+/-0.04 microM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-beta-D-xylopyranoside or chlorate reduced spermine uptake consid...

Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fastin...

1 We studied the interaction between the naturally occurring polycation spermine (SPERM) and 2 Na-exchanged SWy-2 Wyoming montmorillonite (Na-SWy-2 Mt) and between spermine3 exchanged montmorillonite (Mt-SPERM) and the herbicide fluometuron. Mt-SPERM with 4 spermine contents ranging between 0 and 1.2 times the cation exchange capacity (CEC) of 5 Na-SWy-2 were studied by XRD, FTIR and TGA analys...

Spermine, a cellular polyamine, down-regulates O2- generation in human neutrophils stimulated by receptor-linked agonist [Ogata, Tamura and Takeshita (1992) Biochem. Biophys. Res. Commun. 182, 20-26]. In this study, to elucidate the mechanism for the inhibition, the effect of spermine on cell-free activation of the O2- generating enzyme (NADPH oxidase) was examined. Spermine suppressed the SDS-...

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of s...