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Accueil > Publications > Recherche par années > Années 2000 > 2000

2000

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Replacement of an NH3 by an iminoether in transplatin makes an antitumor drug from an inactive compound

To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH3 by an iminoether group, trans-[PtCl2Z-HN=C(OMe)Me( NH3)] and trans-[PtCl2E-HN=C(OMe)Me(NH3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC50 values being 103, 37, and 215 muM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice.

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Replacement of glycine with dicarbonyl and related moieties in analogues of the C-terminal pentapeptide of cholecystokinin : CCK2 agonists displaying a novel binding mode

Recent advances in the field of cholecystokinin have indicated the possible occurrence of multiple affinity states of the CCK2 receptor. Besides, numerous pharmacological experiments performed "in vitro" and "in vivo" support the eventuality of different pharmacological profiles associated to CCK2 ligands. Indeed, some agonists are essentially anxiogenic and uneffective in memory tests, whereas others are not anxiogenic and appear as able to reinforce memory. The reference compound for the latter profile is the CCK-8 analogue BC 264 (Boc-Tyr(SO3H)-gnle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2).

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Spacer length dependence on the efficiency of dimeric anionic peptides in gene transfer by glycosylated polylysine/plasmid complexes

Amphiphilic anionic peptides have been used to enhance the efficiency of transfection by helping plasmids to escape from endosomes to the cytosol, It has been shown that efficiency of an eicosamers containing five glutamyl residues (E5), can be considerably enhanced either by transforming it into a dimer or by adding a tripeptide WYG in a C-terminal position (E5WYG). The dimerization of the peptide E5WYG leads to a more efficient tool when the dimerization device includes the tripeptide WYG unit and a longer spacer arm made of Gly-ß Ala-ß Ala residues. but to a 10-fold less efficient tool when the dimerization device includes a shorter spacer, a glycyl residue. Both dimers are taken up by the calls to a similar extent. Both dimers seem to be surrounded similarly as far as the environmental pH is concerned. In contrast, we found a correlation between the propensity of the peptides to adopt a helical structure at neutral pH and the gene transfer efficiency.

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Spectroscopic studies on ethidium bromide binding to intramolecular parallel and antiparallel triple helices containing T*A : T and G*G : C triplets

The interaction of ethidium bromide (EB), a DNA intercalator, with two intramolecular triplexes (5)’d(G(4)A(4)G(4)-[T-4]-C4T4C4-[T-4]-G(4)T(4)G(4)), (5)’d(G(4)T(4)G(4)-[T-4]-G(4)A(4)G(4)-[T-4]-C4T4C4) ([T-4] represents a stretch of 4 thymine residues) and their precursor duplexes has been investigated by circular dichroism, fluorescence and UV absorption spectroscopy. Binding of EB induces a circular dichroism band in the region around 310 nm which is positive for the duplex forms but negative for the tripler forms. We observed that the binding of EB to the duplex form does not induce the formation of the tripler structures. Thermal denaturation experiments demonstrate that EB stabilizes more the parallel triple helix than the antiparallel one. Analysis of the binding process from fluorescence measurements shows that binding constants to the triple helical forms and to the hairpin reference duplex [T-4]-G(4)A(4)G(4)-[T-4]-C4T4C4) are close. However the binding site size is larger for the triplexes (4-6 base triplets) than for the duplex (2 base pairs).

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Spectroscopic study of the hydration equilibria and water exchange dynamics of lanthanide(III) complexes of 1,7-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (DO2A)

The hydration state of a series of [Ln(DO2A)(H2O)(n)](+) complexes in aqueous solution at pH = 6.4-7.0 was studied by measuring the lanthanide-induced O-17 shifts (LIS) of water [Ln includes elements from Ce to Yb ; DO2A = 1,7-bis(carboxymethyl)-1,4,7, 10-tetraazacyclododecane]. Their contact contribution, obtained from Reilley plots, indicated a decrease in the inner-sphere water coordination number of the [Ln(DO2A)(H2O)(n)]+ complexes from n = 3 (Ce-Eu), to n = 2 (Tb-Yb). A temperature-dependent UV/Vis absorption study of the 578-582 nm F-7(0) —> D-5(0) transition band of [Eu(DO2A)(H2O)(n)](+) in aqueous solution showed that this complex is present in an equilibrium between eight- and nine-coordinate species with n = 2 and n = 3, respectively.

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Structure prediction of the dimeric neu/ErbB-2 transmembrane domain from multi-nanosecond molecular dynamics simulations

Dimerization of the neu/ErbB-2 receptor tyrosine kinase is a necessary but not a sufficient step for signaling. Despite the efforts expended to identify the molecular interactions responsible for receptor-receptor contacts and particularly those involving the transmembrane domain, structural details are still unknown. In this work. molecular dynamics simulations of the helical transmembrane domain (TM) of neu and ErbB-2 receptors are used to predict their dimer structure both in the wild and oncogenic forms.

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Synthetic approaches to C-glucosinolates

In these pages, short and efficient synthetic approaches to C-analogs of glucosinolates are described. Starting from D-glucose, C-glucotropaeolin (6) and C-glucocapparin (11) were synthesized in three steps. Preliminary enzymatic assays involving sulfatase and myrosinase have been performed. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

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