We studied the interactions of a tau derived hexapeptide AcPHF6 with β-amyloid peptides Aβ40 and Aβ42 which reveals its unusual ability to promote Aβ fibrillogenesis. The results demonstrate that the N-acetylated and C-amidated AcPHF6 hexapeptide can cause significant acceleration in Aβ40 and Aβ42 fibril growth. Aggregation kinetic studies at pH 7.4 show that at 25 μM, AcPHF6 hexapeptide was able to cause ∼2.3-fold increase in Aβ40 fibrillogenesis dramatically changing the aggregation kinetics. In addition, AcPHF6 peptide was able to reduce cellular toxicity mediated by Aβ40 and Aβ42 in hippocampal neuronal cell line (HT22). Computational studies suggest that the AcPHF6 peptide can act as an anchor and provides a hydrophobic surface for Aβ monomer to bind and undergo rapid fibrillogenesis to form less toxic fibrils and alter the aggregation kinetics. At the molecular level we propose a "dock-and-pack" mechanism where the AcPHF6 hexapeptide aggregates can stabilize the β-hairpin and promote rapid Aβ self-assembly and growth to form less toxic oligomers or fibrils. Our results have direct implications in designing novel peptide/peptidomimetics as novel pharmacological tools to study protein aggregation and potentially prevent Aβ-mediated toxicity in Alzheimer's disease.
The effect of variation in the length of surfactant hydrocarbon tail groups was tested in a series of dissymmetric gemini surfactants (N-alkyl N,N,N,N-tetramethyl-N-(6-pyren-6yl)-hexyl)propane-1,3-diammonium dibromide designated as CCCBr, with m = hexyl pyrene, and n = 8, 12, 14, 16, and 18. The aggregation properties of these surfactants have been investigated by means of H NMR, fluorescence spectroscopy, surface tension and electrical conductivity measurements. The critical micelle concentration (CMC) was determined using surface tension and confirmed using the specific conductance method. Krafft temperatures and the degree of micelle ionization (α) were obtained from specific conductance measurements. With an increase of the dissymmetry (m/n) ratio, the CMC decreased linearly and an increase in the Krafft temperatures was observed for all of the gemini surfactants. α values for the dissymmetric GS were higher than those of the m-3-m counterparts, which may be attributed to enhanced micelle-micelle interactions that arise from increased hydrophobicity of the hydrocarbon chains. The introduction of the bulky pyrenyl tail group resulted in much lower CMC values compared to their symmetrical counterparts affecting the packing of these surfactants at the air/water interface, which resulted in high-ordered structures (lamellar and inverted micelles). This in turn affected the thermodynamic parameters of the micellization.
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Green chemistry which is the latest and one of the most researched topics now days has been in demand since 1990’s. Majority of research in green chemistry aims to reduce the energy consumption required for the production of desired product whether it may be any drug, dyes and other chemical compounds. It aims to reduce or even eliminates the production of any harmful bi-products and maximizing the desired product without compromising with the environment. The three key developments in green chemistry include use of super critical carbon di oxide as green solvent, aqueous hydrogen peroxide as an oxidizing agent and use of hydrogen in asymmetric synthesis. It also focuses on replacing traditional methods of heating with that of modern methods of heating like microwave radiations so that carbon footprint should be reduces as low as possible. This review emphasize on principle, methodology and recent applications of green chemistry. © 2011 IGJPS. All rights reserved.
Suzuki cross coupling reaction is one of the most famous reaction in the field of chemistry. It is a very effective method for making carbon – carbon bonds. It has been extensively utilized in the synthesis of many carbon molecules including the most complex ones. It also find application in the synthesis of compounds of biological sources like (+)-dynemicin, Adragmacidin F, Flurbiprofen, Felbinac, Fenbufen, Difunisal, Aporphinoids, Oximidine II, Nemertelline, Gymnocin A, Palytoxin, Michellamine, CP263,114, Halenaquinone, Brevetoxin, Yuehchukene, caparratriene etc which have been synthesized using the same reaction along with some other organic compounds. The present review article emphasis on carbon-carbon bond formation via cross coupling reaction, mechanism and applications in a natural product synthesis. © 2011 IGJPS. All rights reserved
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