Solid‐Phase Combinatorial Synthesis and Biological Evaluation of Destruxin E Analogues

The solid‐phase combinatorial synthesis of cyclodepsipeptide destruxin E has been demonstrated. The combinatorial synthesis of cyclization precursors 8 was achieved by using a split and pool method on SynPhase Lanterns. The products were successfully macrolactonized in parallel in the solution phase by using 2‐methyl‐6‐nitrobenzoic anhydride and 4‐(dimethylamino)pyridine N‐oxide to afford macrolactones 9 , and the subsequent formation of an epoxide in the side chain gave 18 member destruxin E analogues 6 . Biological evaluation of analogues 6 indicated that the N‐MeAla residue was crucial to the induction of morphological changes in osteoclast‐like multinuclear cells (OCLs). Based on structure–activity relationships, azido‐containing analogues 15 were then designed for use as a molecular probe. The synthesis and biological evaluation of analogues 15 revealed that 15 b , in which the Ile residue was replaced with a Lys(N₃) residue, induced morphological changes in OCLs at a sufficient concentration, and modification around the Ile residue would be tolerated for attachment of a chemical tag toward the target identification of destruxin E ( 1 ).     

The first total synthesis and structural determination of antibiotics K1115 B1s (alnumycins)

K1115 B₁, isolated from the broth of Streptomyces species, was found to be a mixture of stereoisomers. Authors synthesized all stereoisomers of K1115 B₁ by convergent synthesis coupling a rhamnose derivative, an isobenzofuranone, and a chiral tetraol. Comparison of ¹H NMR spectra and optical rotations made it clear that the absolute structures of K1115 B_1α (the major isomer) and K1115 B_1β (the minor isomer) were (1R, 17S)- and (1R, 17R)-configurations, respectively. The optical rotations of the stereoisomers revealed that alnumycin, reported as the identical structure with K1115 B₁, might be another mixture of stereoisomers.     

Photoinduced nitric oxide release from a nitrobenzene derivative in mitochondria

We report a novel NO donor (RpNO), containing a 2,6-dimethylnitrobenzene moiety for photocontrollable NO release and a rhodamine moiety for targeting to mitochondria. Photorelease of NO from RpNO in aqueous solution was confirmed by means of ESR analysis. Cellular release of NO from RpNO was confirmed with the aid of DAF-FM DA, an NO-specific fluorescence probe. RpNO was colocalized with MitoTracker Green FM, a mitochondrial stain, in HCT116 colon cancer cells and exhibited photodependent cytotoxicity. Our results indicate that RpNO is an effective NO donor for time-controlled, mitochondria-specific NO treatment.     

Mapping of the primary mannose binding site of pradimicin A

Pradimicin A (PRM-A) is an actinomycete-derived antibiotic with the lectin-like property of being able to recognize D-mannopyranoside (Man) in the presence of Ca(2+) ion. PRM-A and its derivatives have been attracting a great deal of attention as the only family of natural carbohydrate receptors with nonpeptidic skeleton and, more recently, as conceptually novel drug candidates for human immunodeficiency virus (HIV). Despite its scientific interest and potential therapeutic importance, understanding how PRM-A recognizes Man has been severely limited. Conventional interaction analysis of PRM-A with Man in solution has been frustrated by aggregation of PRM-A and the three-component equilibrium consisting of the [PRM-A(2)/Ca(2+)], [PRM-A(2)/Ca(2+)/Man(2)], [PRM-A(2)/Ca(2+)/Man(4)] complexes, and their mixed oligomers. In this Article, we demonstrate the interaction analysis of PRM-A with methyl α-D-mannopyranoside (Man-OMe) in the solid state, which benefits from aggregate-forming propensity of PRM-A and eliminates the problem associated with the complicated equilibrium in solution. Isothermal titration calorimetry (ITC) analysis and coprecipitation experiments revealed that the primary Man binding of PRM-A is markedly tighter than the secondary one, leading to preparation of the solid aggregate solely composed of the [PRM-A(2)/Ca(2+)/Man-OMe(2)] complex. The simple 1:1 complexes of biosynthetically (13)C-enriched PRM-As and [(13)C(6)]Man-OMe facilitated the analysis of the primary Man binding of PRM-A by two-dimensional dipolar-assisted rotational resonance (2D-DARR), which clearly identified that the cavity consisted of D-alanine moiety and ABC rings of PRM-A is the Man binding site. Interestingly, the proposed Man binding site of PRM-A seems to resemble the typical architecture of artificial carbohydrate receptors.     

Virtual screening for ligands of the insect molting hormone receptor

Insect growth is regulated by the orchestrated event of ecdysteroids and their receptor proteins. Agonists/antagonists of ecdysteroid receptor are predicted to disrupt normal growth, providing good candidates of new insecticides. A database of over 2 million compounds was subjected to a shape-based virtual screening cascade to identify novel nonsteroidal hits similar to the known EcR ligand ponasterone A. Testing revealed micromolar hits against two strains of insect cells. Docking experiments against EcR were used to support the predicted binding mode of these ligands based on their overlay to ponasterone A.     

High proton conduction in a chiral ferromagnetic metal-organic quartz-like framework

A complex-as-ligand strategy to get a multifunctional molecular material led to a metal-organic framework with the formula (NH(4))(4)[MnCr(2)(ox)(6)]·4H(2)O. Single-crystal X-ray diffraction revealed that the anionic bimetallic coordination network adopts a chiral three-dimensional quartz-like architecture. It hosts ammonium cations and water molecules in functionalized channels. In addition to ferromagnetic ordering below T(C) = 3.0 K related to the host network, the material exhibits a very high proton conductivity of 1.1 × 10(-3) S cm(-1) at room temperature due to the guest molecules.     

Spatiotemporally controlled contraction of micropatterned skeletal muscle cells on a hydrogel sheet

We have developed gel sheet-supported C(2)C(12) myotube micropatterns and combined them with a microelectrode array chip to afford a skeletal muscle cell-based bioassay system. Myotube line patterns cultured on a glass substrate were transferred with 100% efficiency to the surface of fibrin gel sheets. The contractile behavior of each myotube line pattern on the gel was individually controlled by localized electrical stimulation using microelectrode arrays that had been previously modified with electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT). We successfully demonstrated fluorescent imaging of the contraction-induced translocation of the glucose transporter, GLUT4, from intracellular vesicles to the plasma membrane of the myotubes. This device is applicable for the bioassay of contraction-induced metabolic alterations in a skeletal muscle cell.     

Fabrication and evaluation of photonic metamaterial crystal

Many researching efforts have been reported to seek various fundamental LC resonance structures, recently. But still the Split Ring Resonator (SRR) is the most famous and major fundamental LC-resonance structure used in the metamaterial. We employed SRR structure as the fundamental LC-resonance mechanism to fabricate photonic crystal with periodic arrangement of two different metamaterial areas composed from SRR arrays on the dielectric substrate. We developed Photonic Metamaterial Crystal (PMC) to realize the more advanced and versatile functions of the metamaterial by 1 dimensional or 2 dimensional periodic arranging of two metamaterial sections which have different dispersion properties due to the different size of SRR structures each other. In this paper, we report the fabrication process, estimation of PMC properties and some possible future application prospects, for instance the PMC waveguide structures and nonlinear properties of PMC observed as selective LC-resonant properties in Raman mapping analysis of PMC. These are quite interesting characters of PMC and the attractive applications as the PMC devices.     

Proposal of a frequency-synthesis chain between the microwave and optical frequencies of the Ca intercombination line at 657 nm using diode lasers

We propose a frequency synthesis chain which can directly connect a microwave atomic clock with a visible laser. We design this chain for the frequency measurement of a visible laser locked on the intercombination transition of Ca at 657 nm. The proposed chain is based on both an optical difference frequency divider and an optical frequency comb generator, and it is designed to use nine visible and near-infrared diode lasers. We discuss the technical requirements to realize the frequency measurement accuracy level of 10^–14.     

Sonochemically synthesized core-shell structured Au–Pd nanoparticles supported on γ-Fe2O3 particles

A sample of Au–Pd bimetallic nanoparticles supported on γ-Fe₂O₃ was synthesized in a sonochemically one-pot process. The structural analyses of the synthesized sample were performed by the techniques of X-ray Absorption Fine Structure (XAFS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and UV–vis spectrometry. Results indicated that the synthesized sample formed a core-shell structure in which a gold core was surrounded by a thin palladium shell. The reaction rate constant for the hydrogenation of cyclohexene of the present sample showed higher value than that of Pd nanoparticles supported on γ-Fe₂O₃ and core-shell structured Au–Pd nanoparticles supported on SiO₂. The present sample is a promising catalyst material which has a high catalytic activity.