Mycosamine orientation of amphotericin B controlling interaction with ergosterol: sterol-dependent activity of conformation-restricted derivatives with an amino-carbonyl bridge

Amphotericin B (AmB 1) is known to assemble together and form an ion channel across biomembranes. The antibiotic consists of mycosamine and macrolactone moieties, whose relative geometry is speculated to be determinant for the drug's channel activity and sterol selectivity. To better understand the relationship between the amino-sugar orientation and drug's activity, we prepared conformation-restricted derivatives 2-4, in which the amino and carboxyl groups were bridged together with various lengths of alkyl chains. K+ influx assays across the lipid-bilayer membrane revealed that ergosterol selectivity was markedly different among derivatives; short-bridged derivative 2 almost lost the selectivity, while 3 showed higher ergosterol preference than AmB itself. Monte Carlo conformational analysis of 2-4 based on NOE-derived distances indicated that the amino-sugar moiety of 2 comes close to C41 because of the short bridge, whereas those of 3 and 4 are pointing outward. The mutual orientation of the amino-sugar moiety and macrolide ring is so rigid in derivatives 2 and 3 that these conformations should be unchanged upon complex formation in lipid membranes. These results strongly suggest that the large difference in sterol preference between derivatives 2 and 3 is ascribed to the different orientation of amino-sugar moieties. These findings allowed us to propose a simple model accounting for AmB-sterol interactions, in which hydrogen bonding between 2'-OH of AmB and 3beta-OH of ergosterol plays an important role.     

Purification of enzymes by high-speed gel filtration on TSK-GEL SW columns

The purification of enzymes was investigated by high-speed gel filtration on TSK-GEL G3000SWG columns packed with porous silica gel deactivated by chemically bonded hydrophilic compounds. Crude β-galactosidase from bacterial cells and commercial urease were purified ca. 15-fold in a single gel filtration. These enzymes were eluted within an hour from the column and the recoveries of enzymatic activity were almost 100% although the operation was carried out at room temperature (22°). Samples up to 100 mg could be applied to the column without loss of separation efficiency.     

Theory of the structural fluctuation of Au55 clusters

Stabilities and structural fluctuations of both neutral and charged Au₅₅ clusters are examined and discussed in relation to recent experimental observations of small gold particles with an electron microscope. Transition probabilities between the icosahedral and cuboctahedral structures are calculated according to the transition state theory using a model potential consisting of attractive many-body, repulsive pairwise and Coulomb parts. It is shown that for a neutral cluster the cuboctahedral structure has too short life time to be observed around room temperature and that, on the other hand, for more than 6-fold multiply charged clusters, both structures have life times of the order of 0.1 s around room temperature and, therefore, the transition between them can be observed.     

A new synthesis of δ-lactones from oxetanes

Oxetanes were reacted with lithium enolates generated from esters or amides in the presence of boron trifluoride etherate to give δ-hydroxyesters or amides in high yield, which were hydrolyzed and converted to δ-lactones.     

Determination of some dithiocarbamates by catalytic thermometric titration

The determination of dithiocarbamates by catalytic thermometric titration is described. The dithiocarbamates can be determined in the range 0.5-20 mumole with relative errors of about 5%.     

Studies on the biaxial stretching of polypropylene film. III. Electron microscopic observation of the one-step biaxial stretching of isotactic polypropylene spherulites

Polypropylene films of various isotacticities and crystallinities were stretched biaxially in one step in air at 140–152°C or polyaxially in poly(ethylene glycol) at 130–160°C, and the morphological changes were studied by electron microscopy (replica). In the initial stage of stretching, with v_A = 1.4, the spherulites of one of the films used for the experiment were broken both from the centers and boundaries, and those of another film were broken mainly from the center. This difference in the deformation behavior seems to be characteristic of the film properties and independent of the method of stretching, although the factors involved are still unknown. On further stretching (v_A = 22), well annealed spherulites were broken into many small blocklike fragments with unfolded fibrils running among them, particularly at the low stretching temperature (140°C), and fibrillation proceeded at the expense of the residual fragments. In the case of quenched or slightly crystallized material, the fragments were dendritic and divided into finer and finer fibrils on stretching. At elevated temperature, however, even for well annealed spherulites, the deformation behavior resembles that of the quenched material, and at a high degree of stretching the spherulites take on the fibrillar net structure in every case. In films containing a high amount of atactic fraction, radial, tangential, and boundary cracking occurred more easily, and broad fibrils were observed across the cracks.     

Selective ablation of atherosclerotic lesions with less thermal damage by controlling the pulse structure of a quantum cascade laser in the 5.7-µm wavelength range

Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.     

Second-harmonic-generation microscope using eight-segment polarization-mode converter to observe three-dimensional molecular orientation

We developed a compact polarization-mode converter for microscopy to control three-dimensional polarization at the focus. The converter consisted of two homogeneously aligned liquid-crystal spatial light modulators with eight independently controllable electrodes (segments), and a quarter-waveplate. The converter converted a linearly polarized beam to three polarization modes: two orthogonal linear polarizations and a pseudo-radial polarization. We applied the converter to second-harmonic-generation microscopy and demonstrated the detection of three-dimensional molecular orientation.     

Blue emission from InGaN/GaN hexagonal pyramid structures

Cathodoluminescence (CL) from InGaN grown on GaN hexagonal pyramid structures has been investigated. The facet structure can be controlled by the growth temperature and reactor pressure. GaN pyramid structures surrounded with facets were grown at 1020 C at a pressure of 500 Torr by low-pressure metalorganic vapor phase epitaxy (LP-MOVPE). The indium mole fraction in the InGaN film depends on the facet structure. The thickness of the InGaN and the peak wavelength and intensity of the CL from the InGaN gradually increased from the bottom to the top of the facets.