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Promising Molecule (promising + molecule)
Selected AbstractsThe Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004Claudia Link Abstract A 2-kDa synthetic derivative of the macrophage-activating lipopeptide (MALP-2) from Mycoplasma fermentans is a potent inducer of monocytes/macrophages and improves the immunogenicity of antigens co-administered by systemic and mucosal routes. Dendritic cells (DC) are the most potent antigen-presenting cells, which are able to prime naive T cells in vivo. To elucidate the underlying mechanisms of MALP-2 adjuvanticity, we analyzed its activity on bone marrow-derived murine DC. In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules. MALP-2 also enhances the secretion of cytokines (IL-1,, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells. Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity. Thus, the adjuvanticity of MALP-2 can be mediated, at least in part, by the stimulation of DC maturation, which in turn leads to an improved antigen presentation. Therefore, MALP-2 is a promising molecule for the development of immune therapeutic or prophylactic interventions. [source] Multilevel Biomemory Device Consisting of Recombinant Azurin/Cytochrome cADVANCED MATERIALS, Issue 4 2010Taek Lee A multilevel biomemory device displays two pairs of nonvolatile write, read, and erase functions (see figure). The device consists of recombinant azurin/cytochrome c. Azurin is recombined with a cysteine residue to enhance the stability of the self-assembled protein on a gold surface. Then, cytochrome c is adsorbed onto the immobilized azurin layer. The verified memory characteristic of the proposed device implies that the metalloprotein is a very promising molecule for the development of a new type of memory device. [source] 3- O -methylfunicone, a metabolite of Penicillium pinophilum, inhibits proliferation of human melanoma cells by causing G2 + M arrest and inducing apoptosisCELL PROLIFERATION, Issue 4 2009A. Baroni Objectives:, Melanoma cells take advantage of impaired ability to undergo programmed cell death in response to different external stimuli and chemotherapeutic drugs; this makes prevention of tumour progression very difficult. The aim of this study was to demonstrate whether 3- O -methylfunicone (OMF), a metabolite of Penicillium pinophilum, has the ability to arrest cell population growth and to induce apoptosis in A375P (parental) and A375M (metastasis derivatived) melanoma cell lines. Materials and methods:, Cell proliferation and apoptosis were analysed by flow cytometry, DNA fragmentation, caspase-3 and caspase-9 activation, and PARP-1 cleavage. Results:, We demonstrated that OMF affected cell proliferation in a time- and dose-dependent manner, reaching the best effect at concentration of 80 µg/ml for 24 h. Flow cytometry revealed that OMF caused significant G2 phase arrest, which was associated with marked decrease in cyclin B1/p34cdc2 complex and p21 induction. OMF also induced marked decrease of survivin expression. Reduced levels of apoptosis were evident after silencing p21 expression in both cell lines. Finally, the effect exercised by OMF on hTERT and TEP-1 gene expression confirmed the ability of this molecule to interfere with replicative ability of cells. Conclusions:, The results reported here seem to suggest that OMF as a promising molecule to include in strategies for treatment of melanoma. [source] Targeting the c-Myc coiled coil with interfering peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 9 2008Eva M. Jouaux Abstract c-Myc is one of the most frequently deregulated oncogenes in human cancers, and recent studies showed that even brief inactivation of Myc can be sufficient to induce tumor regression or loss. Consequently, inactivation of Myc provides a novel therapeutic opportunity and challenge, as the dimerization of Myc with Max is crucial for its function. We applied two strategies to specifically target this coiled coil mediated interaction with interfering peptides: a dominant-negative human Max sequence (Max) and a peptide selected from a genetic library (Mip). Both peptides form coiled coils and were fused to an acidic extension interacting with the basic DNA-binding region of human Myc. The genetic library was obtained by semi-rational design randomizing residues important for interaction, and selection was carried out using a protein-fragment complementation assay. The peptides Max and Mip easily outcompeted the human Myc:Max interaction and successfully interfered with the DNA binding of the complex. Both interfering peptides exhibited higher Tm (,Tm = 13 and 15 °C) upon interaction with Myc compared to wt Max. The inhibitory effect of the two interfering peptides on human Myc:Max activity makes them promising molecules for analytical and therapeutic Myc-directed research. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Dendritic macromolecules at the interface of nanoscience and nanotechnologyMACROMOLECULAR SYMPOSIA, Issue 1 2003Jean M.J. Fréchet Abstract As a result of their unique architecture and structural as well as functional versatility, dendrimers have generated considerable interest in numerous areas of the physical sciences, engineering, as well as the biological sciences. Both their size - in the 1-10 nm range - and their globular shape resemble those of many proteins suggesting a host of biomimetic and nanotechnological applications. This brief highlight describes some of our recent work with nascent applications of dendrimers as unimolecular nanoreactors, as nanoscale antennae for energy harvesting and transduction, and as nanosized carriers for diagnostic or therapeutic applications. While implementation of some of these applications may still be distant, the impatient critic might remember that new markets are not created overnight as demonstrated by the slow commercial acceptance of many promising molecules and technologies with development frequently extending decades after their initial discovery. [source] Exhaustive Structure Generation for Inverse-QSPR/QSARMOLECULAR INFORMATICS, Issue 1-2 2010Tomoyuki Miyao Abstract Chemical structure generation based on quantitative structure property relationship (QSPR) or quantitative structure activity relationship (QSAR) models is one of the central themes in the field of computer-aided molecular design. The objective of structure generation is to find promising molecules, which according to statistical models, are considered to have desired properties. In this paper, a new method is proposed for the exhaustive generation of chemical structures based on inverse-QSPR/QSAR. In this method, QSPR/QSAR models are constructed by multiple linear regression method, and then the conditional distribution of explanatory variables given the desired properties is estimated by inverse analysis of the models using the framework of a linear Gaussian model. Finally, chemical structures are exhaustively generated by a sophisticated algorithm that is based on a canonical construction path method. The usefulness of the proposed method is demonstrated using a dataset of the boiling points of acyclic hydrocarbons containing up to 12 carbon atoms. The QSPR model was constructed with 600 hydrocarbons and their boiling points. Using the proposed method, chemical structures which had boiling points of 100, 150, or 200,°C were exhaustively generated. [source] | |||||||||||||