Identification of Novel Rab27a/Melanophilin Blockers by Pharmacophore-Based Virtual Screening

Melanocytes are unique cells that produce specific melanin-containing intracellular organelles called melanosomes. Melanosomes are transported from the perinuclear area of melanocytes toward the plasma membrane as they become more melanized in order to increase skin pigmentation. In this vesicular trafficking of melanosomes, Rab27a, melanophilin, and myosin Va play crucial roles in linking melanosomes to actin-based motors. To identify novel compounds to inhibit binding interface between Rab27a and melanophilin, a pharmacophore model was built based on a modeled 3D structure of the protein complex that describes the essential binding residues in the intermolecular interaction. A pharmacophore model was employed to screen a chemical library database. Finally, 25 virtual hits were selected for biological evaluations. The biological activities of 11 analogues were evaluated in a second assay. Two compounds were identified as having concentration-dependent inhibitory activity. By analyzing structure–activity relationships of derivatives of BMD-20, two hydroxyl functional groups were found to be critical for blocking the intermolecular binding between Rab27a and melanophilin.     

Indium trichloride mediated intramolecular Prins-type cyclization

[reaction: see text] Intramolecular Prins-type reactions of compounds having both functionalities of homoallyl alcohol and acetal moiety are described. The intramolecular Prins cyclizations were performed using indium trichloride in chloroform or 25% aqueous THF. Both 9-oxabicyclo[3.3.1]nonane and 3,9-dioxabicyclo[3.3.1]nonane compounds were successfully obtained in moderate yields.     

Fabrication of nano-structured polythiophene nanoparticles in aqueous dispersion

The synthetic route of unsubstituted polythiophene (PT) nanoparticles was investigated in aqueous dispersion via Fe³⁺-catalyzed oxidative polymerization. With this new synthetic method, high conversion of thiophene monomers was obtained with only a trace of FeCl₃. The dispersion state showed that the PT nanoparticles were well dispersed in many polar solvents, compared to non-polar solvents, such as acetone, chloroform, hexane, and ethyl acetate. To compare the photoluminescence properties between PT nanoparticle dispersion and PT bulk polymers, the PL intensities were measured in the same measuring conditions. Further, core–shell poly(styrene/thiophene) (poly(St/Th)) latex particles were successfully prepared by Fe³⁺-catalyzed oxidative polymerization during emulsifier-free emulsion polymerization. The different polymerization rates of each monomer resulted in core–shell structure of the poly(St/Th) latex particles. The PL data of the only crumpled shells gave evidence that the shell component of core–shell poly(St/Th) latex particles is indeed PT, which was corroborated by SEM data. PL intensity of the core–shell poly(St/Th) nanoparticle dispersion was much higher than that of the PT nanoparticle dispersion, due to its thin shell layer morphology, which was explained by the self-absorption effect.     

Synthesis and nonlinear optical properties of novel Y‐type polyester containing tricyanovinylthiazolylazoresorcinoxy group with enhanced thermal stability of dipole alignment

Novel Y‐type polyester 4 containing 5‐methyl‐4‐{5‐(1,2,2‐tricyanovinyl)‐2‐thiazolylazo}resorcinoxy groups as nonlinear optical (NLO) chromophores, which are parts of the polymer backbone, was prepared, and its NLO properties were investigated. Polyester 4 is soluble in common organic solvents such as N,N‐dimethylformamide and dimethylsulfoxide. Polymer 4 shows a thermal stability up to 250 °C from thermogravimetric analysis with glass‐transition temperature obtained from differential scanning calorimetry of approximately 94 °C. The second harmonic generation (SHG) coefficient (d₃₃) of poled polymer film at 1560‐nm fundamental wavelength is 8.12 × 10^?9 esu. The dipole alignment exhibits a thermal stability even at 6 °C higher than glass‐transition temperature (T_g), and no significant SHG decay is observed below 100 °C due to the partial main‐chain character of polymer structure, which is acceptable for NLO device applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011