Hiroyuki Minamikawa

Morphological control of helical solid bilayers in high-axial-ratio nanostructures through binary self-assembly

Mixed molecular species of cardanyl glucoside derived from renewable resources provide nanotubes upon self-assembly in water, while the saturated homologue generated a twisted fibrous morphology. The cardanyl glucoside mixture was fractionated into four individual components in order to study their contribution to the nanotube formation. The rational control of self-assembled helical morphologies was achieved by binary self-assembling of the saturated and monoene derivatives. This method can generate a diversity of self-assembled high-axial-ratio nanostructures (HARNs), ranging from twisted ribbons and helical ribbons to nanotubes.

Nature-like synthetic alkyl branched-chain glycolipids: a review on chemical structure and self-assembly properties

This review presents the structure/property relationship of two classes of synthetic branched-chain glycolipids, namely the Guerbet and isoprenoid glycosides, in particular highlighting the importance of chain branching to their self-assembly properties. Alkyl chain branching in glycolipids tends to stabilise the reversed type phases as well as a lamellar (Lα) phase. These glycolipids exhibit several reversed bicontinuous cubic phases ( ), the reversed hexagonal phase (H II) and the lamellar phase. The detailed structures of the phases are governed by the balance between the hydrophobic chain bulkiness and the headgroup interaction, including hydrogen bonding. Among the isoprenoid glycolipids, an aqueous isoprenoid xyloside exhibits a bicontinuous cubic phase with a diamond (Pn3m) space group at full hydration and that of a glucoside adopts the stable reversed micellar cubic phase of an Fd3m space group. In the series of Guerbet glycolipids, the ones with longer chains may form stable bicontinuous cubic phases (diamond and Schwarz primitive) in dry condition, as well as the gyroid (Ia3d) in excess water. The phase behaviours of these synthetic glycolipids are comparable to those observed in other natural glycolipids, thus making them potentially useful for applications in both nano-electronics and biomedicine, as therapeutic delivery systems.

Confinement Effect of Organic Nanotubes Toward Green Fluorescent Protein (GFP) Depending on the Inner Diameter Size

Transportation, release behavior, and stability of a green fluorescent protein (GFP, 3x4 nm) in self-assembled organic nanotubes with three different inner diameters (10, 20, and 80 nm) have been studied in terms of novel nanocontainers. Selective immobilization of a fluorescent acceptor dye on the inner surface enabled us to not only visualize the transportation of GFP in the nanochannels but to also detect release of the encapsulated GFP to the bulk solution in real time, based on fluorescence resonance energy transfer (FRET). Obtained diffusion constants and release rates of GFP markedly decreased as the inner diameter of the nanotubes was decreased. An endo-sensing procedure also clarified the dependence of the thermal and chemical stabilities of the GFP on the inner diameters. The GFP encapsulated in the 10 nm nanochannel showed strong resistance to heat and to a denaturant. On the other hand, the 20 nm nanochannel accelerated the denaturation of the encapsulated GFP compared with the rate of denaturation of the free GFP in bulk and the encapsulated GFP in the 80 nm nanochannels. The confinement effect based on rational fitting of the inner diameter to the size of GFP allowed us to store it stably and without denaturation under high temperatures and high denaturant concentrations.

Controllable biomolecule release from self-assembled organic nanotubes with asymmetric surfaces: pH and temperature dependence

The release behavior of fluorescent dyes, oligo DNAs and spherical proteins from self-assembled organic nanotubes having 7-9 nm inner diameters has been studied in terms of novel nanocontainers with high-axial ratios. Both much smaller inner diameters and asymmetric inner and outer surfaces are characteristic of the nanotubes. The acid-dissociation constant (pKa) of the amino groups located at the inner surface and the thermal phase transition temperature (Tg-l) of the nanotube were evaluated based on the pH titration and variable-temperature circular dichroism (CD) spectroscopic experiments, respectively. Each guest was slowly released from both open ends of the nanotube under weak alkaline conditions (pH 8.5), as a result of the decrease in electrostatic attraction between the inner surface and the guests. Elevated temperatures above the obtained Tg-l converted the monolayer membrane of the nanotube from a solid state to a fluid one, promoting the remarkably fast release of the guests. The unique release properties of the nanotube as a nanocontainer with two terminal open ends were compared with those of liposomes that posses a closed hollow space covered with fluid bilayer membranes.

Formation and characterization of planar lipid bilayer membranes from synthetic phytanyl-chained glycolipids.

The formability, current-voltage characteristics and stability of the planar lipid bilayer membranes from the synthetic phytanyl-chained glycolipids, 1, 3-di-O-phytanyl-2-O-(beta-glycosyl)glycerols (Glc(Phyt)(2), Mal(N)(Phyt)(2)) were studied. The single bilayer membranes were successfully formed from the glycolipid bearing a maltotriosyl group (Mal(3)(Phyt)(2)) by the folding method among the synthetic glycolipids examined. The membrane conductance of Mal(3)(Phyt)(2) bilayers in 100 mM KCl solution was significantly lower than that of natural phospholipid, soybean phospholipids (SBPL) bilayers, and comparable to that of 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers. From the permeation measurements of lipophilic ions through Mal(3)(Phyt)(2) and DPhPC bilayers, it could be presumed that the carbonyl groups in glycerol backbone of the lipid molecule are not necessarily required for the total dipole potential barrier against cations in Mal(3)(Phyt)(2) bilayer. The stability of Mal(3)(Phyt)(2) bilayers against long-term standing and external electric field change was rather high, compared with SBPL bilayers. Furthermore, a preliminary experiment over the functional incorporation of membrane proteins was demonstrated employing the channel proteins derived from octopus retina microvilli vesicles. The channel proteins were functionally incorporated into Mal(3)(Phyt)(2) bilayers in the presence of a negatively charged glycolipid. From these observations, synthetic phytanyl-chained glycolipid bilayers are promising materials for reconstitution and transport studies of membrane proteins.

Hydration and molecular motions in synthetic phytanyl-chained glycolipid vesicle membranes.

Proton permeation rates across membranes of a synthetic branch-chained glycolipid, 1,3-di-O-phytanyl-2-O-(beta-D-maltotriosyl)glycerol (Mal3(Phyt)2) as well as a branch-chained phospholipid, diphytanoylphosphatidylcholine (DPhPC) were lower than those of straight-chained lipids such as egg yolk phosphatidylcholine (EPC) by a factor of approximately 4 at pH 7.0 and 25 degrees C. To examine whether degrees of water penetration and molecular motions in Mal3(Phyt)2 membranes can account for the lower permeability, nanosecond time-resolved fluorescence spectroscopy was applied to various membranes of branch-chained lipids (Mal3(Phyt)2, DPhPC, and a tetraether lipid from an extremely thermoacidophilic archaeon Thermoplasma acidophilum), as well as straight-chained lipids (EPC, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and digalactosyldiacylglycerol (DGDG)) using several fluorescent lipids. Degrees of hydration of glycolipids, Mal3(Phyt)2, and DGDG were lower than those of phospholipids, EPC, POPC, and DPhPC at the membrane-water interfaces. DPhPC showed the highest hydration among the lipids examined. Meanwhile, rotational and lateral diffusive motions of the fluorescent phospholipid in branch-chained lipid membranes were more restricted than those in straight-chained ones. The results suggest that the restricted motion of chain segments rather than the lower hydration accounts for the lower proton permeability of branch-chained lipid membranes.

Regio- and stereocontrolled synthesis of d-erythro-sphingosine and phytosphingosine from d-glucosamine

d-erythro-Sphingosine (1) and phytosphingosine (2) have been efficiently synthesized from d-glucosamine by utilizing its whole carbon skeleton and functional groups. In this synthetic route, regioselective alkylation of the epoxy-tosylate 9 was achieved with a copper(I)-catalyzed Grignard reagent to give the key intermediate 10, which was converted to both 1 and 2 via regioselective formation of the iodohydrin 11.

Synthesis of 1,3-di-O-alkyl-2-O-(β-glycosyl)glycerols bearing oligosaccharides as hydrophilic groups

A novel series of synthetic glycolipids, 1,3-di-O-alkyl-2-O-(beta-glycosyl)glycerols, and their efficient synthetic route were proposed. These glyceroglycolipids were synthesized in good overall yields and stereoselectivity in five steps via trichloroacetimidate glycosylation with 1,3-di-O-alkylglycerols. This route was applied to prepare the glycolipids bearing a cello- or malto-oligosaccharide with a definite number of sugar residues from one to six. Thin-layer chromatography, elemental analysis, nuclear magnetic resonance spectroscopy and infrared absorption spectroscopy confirmed that these glycolipids were chemically pure compounds.

Amphiphilic designer nano-carriers for controlled release: from drug delivery to diagnostics

Vesicles formed by self-assembly of lipids and surfactants are increasingly recognised as carriers for drug delivery applications in disease targeting and many other biomedical-related areas, demonstrable by the growing number of significant publications. This manuscript reviews important facets of lipid-based vesicles as drug carriers and their surface modifications to achieve controlled release and selective cell targeting. We cover both the more commonly used ionic phospholipid vesicle carriers and the rapidly growing field of non-ionic vesicles/niosomes using self-assembly of uncharged amphiphilic molecules, which could be formed by using sugar surfactants or glycolipids, sorbitan esters, and polyoxyethylene alkyl ethers. Due to their lower cost, biodegradability, low-toxicity, low-immunogenicity and specific sugar-cell recognition, much attention would be devoted to glycolipid bio-surfactants as potential carriers for targeted delivery. Specifically, our review points to the design consideration of lipid and surfactant nano-carriers based on critical packing parameter, membrane curvature, and the effects of hydrophobic chain structures. We have also dedicated a section of this review to summarise some novel applications of various lipid liquid crystal phases in drug delivery, and how in turn these are related to chemical structures of the lipid entities. The final section of this review outlines the application of lipid vesicles as delivery agents for diagnostic imaging.

A reevaluation of the epimeric and anomeric relationship of glucosides and galactosides in thermotropic liquid crystal self-assemblies

Anomers and epimers α- and β-gluco and -galactosides are expected to behave differently. However, recent results on a series of Guerbet glycosides have indicated similar liquid crystal clearing temperatures for pure β-glucosides and the corresponding α-galactosides. This observation has led to speculation on similarities in the self-assembly interactions between the two systems, attributed to the trans-configuration of the 4-OH group and the hydrophobic aglycon. Previous simulations on related bilayers systems support this hypothesis, by relating this clearing transition temperature to intralayer (sugar-sugar) hydrogen bonding. In order to confirm the hypothesis, the comparison was expanded to include the cis-configurated pair, that is, α-gluco/β-galactoside. A set of α-configurated Guerbet glucosides as well as octyl α-galactoside were prepared and their thermotropic phase behavior studied. The data obtained enabled a complete comparison of the isomers of interest. While the results in general are in line with a pairing of the stereo-isomers according to the indicated cis/trans-configuration, differences within the pairs can be explained based on the direction of hydrogen bonds from a simple modeling study.