The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides D-mannose and D-galactose and the disaccharide D-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties. These libraries revealed a diversity of hard and soft assemblies, including unilamellar spherical, polygonal, and tubular vesicles denoted glycodendrimersomes, aggregates of Janus glycodendrimers and rodlike micelles named glycodendrimer aggregates and glycodendrimermicelles, cubosomes denoted glycodendrimercubosomes, and solid lamellae. These assemblies are stable over time in water and in buffer, exhibit narrow molecular-weight distribution, and display dimensions that are programmable by the concentration of the solution from which they are injected. This study elaborated the molecular principles leading to single-type soft glycodendrimersomes assembled from amphiphilic Janus glycodendrimers. The multivalency of glycodendrimersomes with different sizes and their ligand bioactivity were demonstrated by selective agglutination with a diversity of sugar-binding protein receptors such as the plant lectins concanavalin A and the highly toxic mistletoe Viscum album L. agglutinin, the bacterial lectin PA-IL from Pseudomonas aeruginosa, and, of special biomedical relevance, human adhesion/growth-regulatory galectin-3 and galectin-4. These results demonstrated the candidacy of glycodendrimersomes as new mimics of biological membranes with programmable glycan ligand presentations, as supramolecular lectin blockers, vaccines, and targeted delivery devices.

An accelerated modular synthesis of six libraries containing 29 amphiphilic Janus dendrimers, employed to discover and predict functions via primary structures, is reported. These dendrimers were constructed from a single hydrophobic and a single hydrophilic dendron, interconnected with l-Ala to form two constitutional isomeric libraries, with Gly to produce one library, and with l-propanediol ester to generate two additional constitutional isomeric libraries. They are denoted "single-single" amphiphilic Janus dendrimers. Assemblies obtained by injection of their ethanol solution into water were analyzed by dynamic light scattering and cryogenic transmission electron microscopy. A diversity of complex structures including soft and hard dendrimersomes, cubosomes, solid lamellae, and rod-like micelles were obtained in water. It was discovered that the "single-single" amphiphilic Janus dendrimers containing three triethylene glycol groups in the hydrophilic dendron favored the formation of dendrimersomes. Assemblies in bulk analyzed by differential scanning calorimetry and powder X-ray diffraction revealed that the amphiphilic Janus dendrimers with melting point or glass transition below room temperature self-assemble into soft dendrimersomes in water, while those with higher temperature transitions produce hard assemblies. In the range of concentrations where their size distribution is narrow, the diameter of the dendrimersomes is predictable by the d-spacing of their assemblies in bulk. These results suggested the synthesis of Library 6 containing two simpler constitutional isomeric benzyl ester based amphiphilic Janus dendrimers that self-assemble in water into soft dendrimersomes and multidendrimersome dendrimersomes with predictable dimensions.

A branched side chain pyrogallol[4]arene self-assembles into a previously-unreported cogged hydrogen-bonded nanotube structure in the solid state and self-assembles at the air-water interface on the Langmuir trough.

Stimuli-responsive materials offer new opportunities to resolve long-standing materials challenges and are rapidly gaining pivotal roles in diverse applications. For example, smart protective garments This article is protected by copyright. All rights reserved. 2 that rapidly transport water vapor and autonomously block chemical threats are expected to enable an effective new paradigm of adaptive personal protection. However, the incorporation of these seemingly incompatible properties into a single responsive system remains elusive. Herein, we demonstrate a bistable membrane that can rapidly, selectively, and reversibly transition from a highly breathable state in a safe environment to a chemically protective state when exposed to organophosphate threats such as sarin. Dynamic response to chemical stimuli is achieved through the physical collapse of an ultrathin copolymer layer on the membrane surface, which efficiently gates transport through membrane pores composed of single-walled carbon nanotubes (SWNT). The adoption of nanometer-wide SWNTs for ultrafast moisture conduction enables a simultaneous boost in size-sieving selectivity and water-vapor permeability by decreasing nanotube diameter, thereby overcoming the breathability/protection trade-off that limits conventional membrane materials.Adaptive multifunctional membranes based on this platform greatly extend the active use of a protective garment and present exciting opportunities in many other areas including separation processes, sensing, and smart delivery.

a b s t r a c tThe abnormal deposition of proteins as insoluble plaques is associated with many diseases, including Alzheimer's, Parkinson's and type II diabetes. There is an unmet need for synthetic agents that are able to mediate particular steps in the pathway between soluble proteins in their native unfolded state and their insoluble b-sheet rich aggregates. We have previously reported classes of a-helix mimetic that agonize or antagonize islet amyloid polypeptide aggregation, depending on the presence of a lipid bilayer. Here we investigate a novel mixed benzamide and pyridylamide scaffold that gives improved activity and explores the role of side-chain polarity, backbone rigidity and curvature in inhibiting lipid-catalyzed fibrillization.Ó 2015 Published by Elsevier Ltd.The deposition of protein aggregates (amyloidosis) is a characteristic of the pathology of many disease classes including Alzheimer's, Parkinson's, prion diseases, and type II diabetes. 1-3 Typically, misfolding of the native protein leads to extended and highly stable b-sheet oligomers, which undergo further aggregation to ultimately form proteolysis-resistant fibrils. However, the precise oligomeric intermediates involved in amyloidosis, and the mechanism by which they aggregate remains an unsolved problem. In the case of type II diabetes, the protein that undergoes misfolding is the intrinsically disordered 37-residue hormonal peptide islet amyloid polypeptide (IAPP). We have previously described the role played by membrane-bound aggregates of a-helical intermediate conformers en-route to forming b-oligomers from the intrinsically disordered native structure of IAPP (Fig. 1A). 4 This provides an opportunity to retard amyloidosis by stabilizing or disrupting these a-helical intermediates, thus preventing progression of the disease pathology.The oligobenzamide and oligopyridylamide classes of a-helix mimic provide a scaffold from which the phenol ether substituents accurately reproduce the spatial and angular projection of the sidechains at residues i, i + 3/4 and i + 7 of a natural a-helix (Fig. 1B). [5][6][7][8][9][10][11][12] The transient a-helical domain of IAPP is known to contain multiple cationic side-chains, hence we have utilized benzamide and pyridylamide homo-oligomers with complementary polyanionic carboxylate side-chains for the inhibition of IAPP aggregation. [13][14][15][16] However, the use of exclusively anionic side-chains is an oversimplification: the relevant cationic residues of IAPP (e.g., Arg11 and His18) occupy the (i) and (i + 7) positions, with the intercalated (i + 3/4) residues either lipophilic (Phe15) or neutral and polar (Asn14). 15 Recently we described the incorporation of a lipophilic side-chain in the central (i + 3/4) position, leading to increased potency in the oligopyridylamide series. 17 Here we outline the synthesis of a series of oligobenzamides and mixed benzamidepyridylamide trimeric helix mimetics possessing amphiphilic side-chain substituents (Fig. 1B). We seek to understand the role played by ...