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ABSTRACT: Facially amphiphilic (FA) phenylene ethynylene (PE) polymers that self-assemble in aqueous solution were studied by small-angle X-ray diffraction (SAXD) and found to self-assemble into bilayers with a fully extended backbone. The resulting bilayers have long-range liquid-crystalline order. This self-assembly is programmed into the molecule by placing polar and nonpolar groups at precise locations so that they segregate onto opposite sides of the molecular structure. The absence of FA patterning generated an amorphous sample confirming the importance of this programmed amphiphilicity in the self-assembly process. Facially amphiphilic patterning represents a new design criterion for supramolecular chemistry, illustrated here in the observation of molecular ordering into bilayers reminiscent of self-assembled structures commonly found in biology, including amphiphilic beta-sheet polypeptides and phospholipid bilayers.
Chemistry 04/2006; 12(9):2423-7. · 5.93 Impact Factor
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ABSTRACT: The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.
Proceedings of the National Academy of Sciences 02/2005; 102(2):315-20. · 9.68 Impact Factor
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ABSTRACT: Based on the interpretation of X-ray diffraction data reported for crystals of the poly-L-glutamine-rich 19-peptide D(2)Q(15)K(2), Perutz et al. (Proc. Natl. Acad. Sci. USA 2002, 99, 5591-5595) proposed that hollow, water-filled nanotubes are the basic structural motif of amyloid fibers. We are able to offer an alternative interpretation for the same X-ray diffraction data. Our proposed structure consists of beta-sheets, limited in size in the chain direction that stack at an intersheet distance of 0.83 nm to form cross-beta crystallites. The beta-sheets are composed of individual D(2)Q(15)K(2) molecules hydrogen bonding together in the a direction. The relatively linear interchain amide hydrogen bonds in this growth direction occur at two sites: (i) between neighboring backbone amides and (ii) between adjacent (glutamine) side chain amides decorating both surfaces of the beta sheet. The polyQ sub-lattice unit cell is orthorhombic with parameters a =0.950 nm, b = 1.660 nm, and c = 0.695 nm; contains two beta-sheet segments; and has a calculated density of 1.54 g cm(-3). A key ingredient in the proposed structure is the locking of the Q side chains by hydrogen bonding, which allow high-density packing. In addition, there is evidence suggesting that the D(2)Q(15)K(2) molecules adopt a once-folded hairpin conformation.
Biomacromolecules 6(1):425-32. · 5.48 Impact Factor
