The amyloid beta-protein (1-42) is a major constituent of the abnormal extracellular amyloid plaque that characterizes the brains of victims of Alzheimer's disease. Two peptides, with sequences derived from the previously unexplored C-terminal region of the beta-protein, beta 26-33 (H2N-SNKGAIIG-CO2H) and beta 34-42 (H2N-LMVGGVVIA-CO2H), were synthesized and purified, and their solubility and conformational properties were analyzed. Peptide beta 26-33 was found to be freely soluble in water; however, peptide beta 34-42 was virtually insoluble in aqueous media, including 6 M guanidinium thiocyanate. The peptides formed assemblies having distinct fibrillar morphologies and different dimensions as observed by electron microscopy of negatively stained samples. X-ray diffraction revealed that the peptide conformation in the fibrils was cross-beta. A correlation between solubility and beta-structure formation was inferred from FTIR studies: beta 26-33, when dissolved in water, existed as a random coil, whereas the water-insoluble peptide beta 34-42 possessed antiparallel beta-sheet structure in the solid state. Solubilization of beta 34-42 in organic media resulted in the disappearance of beta-structure. These data suggest that the sequence 34-42, by virtue of its ability to form unusually stable beta-structure, is a major contributor to the insolubility of the beta-protein and may nucleate the formation of the fibrils that constitute amyloid plaque.

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The formation of insoluble proteinaceous deposits is characteristic of many diseases which are collectively known as amyloidosis. There is very little molecular-level structural information available regarding the amyloid deposits due to the fact that the constituent proteins are insoluble and noncrystalline. Therefore, traditional protein structure determination methods such as solution NMR and X-ray crystallography are not applicable. We report herein the application of the solid-state NMR technique rotational resonance (R2) to the accurate measurement of carbon-to-carbon distances in the amyloid formed from a synthetic fragment (H2N-LeuMetValGlyGlyValValIleAla-CO2H) of the amyloid-forming protein of Alzheimer's disease (AD). This sequence has been implicated in the initiation of amyloid formation. Two distances measured by R2 indicate that an unusual structure, probably involving a cis amide bond, is present in the aggregated peptide amyloid. This structure is incompatible with the accepted models of fibril structure. A relationship between this structure and the stability of the amyloid is proposed.

Polyolefins are finding increased popularity in microfluidic applications due to their attractive mechanical, processing, and optical properties. While intricate features are typically realized in these thermoplastics by hot embossing and injection molding, such fabrication approaches are expensive and slow. Here, we apply our shrink-induced approach-first demonstrated with polystyrene 'Shrinky-Dink' sheets-to create micro- and nanostructures with cross-linked polyolefin thin films. These multi-layered films shrink by 95% and with greater uniformity than the Shrinky-Dinks. With such significant reduction in size, along with attractive material properties, such commodity films could find important applications in low cost microfluidic prototyping as well as in point-of-care diagnostics. In this technical note, we demonstrate the ability to rapidly and easily create unique microstructures, increase microarray feature density, and even induce self-assembled integrated metallic nanostructures with these shrink wrap films.

This paper reports the application of the solvent system of lithium bromide in tetrahydrofuran for the disaggregation of protected peptide bound to the Kaiser oxime resin. Fourier-transform infrared spectroscopy is used to characterize the aggregating structure and to follow the disaggregation. The solvation of resin-bound peptide has practical consequences in that the yield of the nucleophilic cleavage of protected peptides from the Kaiser resin is greatly increased. Summary: The title substrates react with a variety of metal catalysts to give metal-dependent product arrays (including tricyclic cyclopropanes and others formally arising from the vinylogous 0-keto carbene 3 shown in 0022-3263/90/ 1965-4518$02.50/0 Scheme I) of both synthetic and mechanistic interest. Stoichiometric quantities of Fischer carbene complexes [e.g., (CO)$r=C(R)(OMe)] react both inter-and intra-IC