Combinatorial synthesis of MUC1 glycopeptides: polymer blotting facilitates chemical and enzymatic synthesis of highly complicated mucin glycopeptides

The chemoselective polymer blotting method allows for rapid and efficient synthesis of glycopeptides based on a "catch and release" strategy between solid-phase and water-soluble polymer supports. We have developed a heterobifunctional linker sensitive to glutamic acid specific protease (BLase). The general procedure consists of five steps, namely (i) the solid-phase synthesis of glycopeptide containing BLase sensitive linker, (ii) subsequent deprotections and the release of the glycopeptide from the resin, (iii) chemoselective blotting of the glycopeptide intermediates in the presence of water-soluble polymers with oxylamino functional groups, (iv) sugar elongations using glycosyltransferases, and (v) the release of target glycopeptides from the polymer platform by selective BLase promoted hydrolysis. The combined use of the solid-phase chemical syntheses of peptides and the enzymatic syntheses of carbohydrates on water-soluble polymers would greatly contribute to the production of complicated glycopeptide libraries, thereby enhancing applicative research. We report here a high-throughput synthetic system for the various types of MUC1 glycopeptides exhibiting a variety of sugar moieties. It is our belief that this concept will become part of the entrenched repertoire for the synthesis of biologically important glycopeptides on the basis of glycosyltransferase reactions in automated and combinatorial syntheses.     

Functional monomers and polymers. LXXI. Conformation and interaction studies of poly-L-lysine derivatives with pendant nucleic acid bases

Copolymers of L -lysine and L -lysine derivatives which contained nucleic acid bases substituted on the N^ε position were synthesized by grafting nucleic acid derivatives onto poly-L -lysine. The conformation and interaction of these copolymers in solution were studied by using spectroscopic measurements. They existed in helical conformation at neutral pH values, and the polymer complex formation among them was examined by ultraviolet (UV) measurements in organic solvents. A decrease in the nucleic acid base content of the copolymers resulted in a decrease in helical structures and also in interactions with the polymer-containing complementary bases.     

Novel chiral macrocycles containing two electronically interacting arylene chromophores

Novel chiral macrocycles consisting of two rigid oligoarylene rods and two chiral spiroindane clips have been synthesized by condensation of spiroindane diols and CF3-activated alpha-omega-difluorooligoaryls. Since a broad variety of planar aromatic macrocycles is known, our non-planar, chiral rings represent a new class of macrocyclic compounds. The first two examples, which contain quaterphenylene and diphenylbithiophene rods, are presented in this communication; for one of them a crystal structure is given. The chiroptical properties of the macrocycles can be interpreted as an interplay of the "intra-rod" helicity of individual oligoarylene rods and the "inter-rod" helicity between both chromophores of the macrocycle. The macrocycles can act as chiral dopands of commercially available, and novel, polymeric nematic liquid crystals (emissive polyfluorenes). The "intra-rod" helicity of individual oligoarylene rods is the main feature in determining the resulting helical twisting power (HTP). The cholestric induction in mesogenic, emissive polyfluorenes is of special interest for a realization of electronic devices that have a circularly polarized electroluminescence. The results are also important for an understanding of larger ensembles of chiral rodlike molecules, especially their pi-pi interactions.     

Practical asymmetric synthesis of (S)-MA20565, a wide-spectrum agricultural fungicide

A practical asymmetric synthesis of a wide-spectrum agricultural fungicide, (S)-MA20565 (1), is described. The convergent synthesis was achieved starting from commercially available 3-(trifluoromethyl)aniline (7) in 44% overall yield through five steps and 2-bromobenzaldehyde (9) in 48% overall yield through four steps, respectively. (S)-O-[1-(3-Trifluoromethylphenyl)ethyl]hydroxylamine (2), a key intermediate of 1, was prepared via ruthenium(II)-catalyzed asymmetric transfer hydrogenation of 1-(3-trifluoromethylphenyl)ethanone (6) followed by chlorination using methanesulfonyl chloride and oxyamination using potassium acetohydroxamate with high level of stereocontrol.     

Linear free energy relationships for carbon-13 NMR chemical shifts of substituted benzoic acids1

In order to examine ¹³C-SCS of substituted benzoic acids, chemical shifts of the acid form (I) and the dissociated form (II) have been obtained separately. Single substituent parameters, σ⁰ or σ⁺ are correlated with the shifts for the carboxyl (δ_co) or ipso carbons (δ_ipso), respectively. Among the available five equations which are developed for the analysis with dual (or divided) substituent parameters (DSP), the Swain-Lupton equation (eqn 3) and the Taft-Swain-Lupton equation (eqn 4) give much better correlations, not only for δ_co and δ_ipso but also for the results for ring carbons (C(2), C(5), C(6)), except for those attached to or neighboured by substituents. It is concluded that the SCS of aromatic compounds are best analyzed with substituent parameters derived from reactions or equilibria on the basis of linear free energy relationships.     

Mitogenic activity of Tulipa gesneriana lectins on mouse and human lymphocytes.

Tulipa gesneriana lectin-erythrocyte (TGL-E) which agglutinates mouse erythrocytes showed a potent mitogenic activity on mouse spleen cells and human peripheral blood lymphocytes, however, TGL-E had only slight mitogenic activity on mouse thymus cells. Its subunit alpha with a molecular weight (MW) of about 26,000 showed a potent mitogenic activity as did that of native lectin, but subunit beta with a MW of about 14,000 showed no activity, indicating that the mitogenic activity of TGL-E originates from subunit alpha. TGL-E stimulated T cell enriched spleen cells which passed through a nylon column, but not spleen cells from a nude mouse or spleen cells treated with anti-Thy 1.2 antibody and complement. Thus, TGL-E stimulates only mouse T cells but not B cells. The other lectin in tulip bulbs, Tulipa gesneriana lectin-yeast showed no mitogenic activity on mouse spleen, thymus cells or human paripheral blood lymphocytes.     

Structure of cypridina biluciferyl,a dimer of cypridina luciferyl radical having bioluminescent activity

Structure of $\text{Cypridina}$ biluciferyl (luciferyl radical dimer), which is produced by chemical oxidation of $\text{C}$. luciferin with such as ferricyanide, was determined to be the symmetric 5,5′-dimer of $\text{C}$. luciferin. It gives light in the presence of $\text{C}$. luciferase, although the bioluminescent rate is very low. We suggest that the biluciferyl is an intermediate in the oxidation of the luciferin to $\text{C}$. luciferinol.     

Ruthenium-catalyzed formation of aryl(diphenyl)phosphine oxides by reactions of propargylic alcohols with diphenylphosphine oxide

1,1-Diaryl-1-penten-4-yn-3-ols react with diphenylphosphine oxide in the presence of a thiolate-bridged diruthenium complex as a catalyst and give high yields of aryl(diphenyl)phosphine oxide products via an initial substitution followed by a cyclization at the produced allene intermediate. [reaction: see text]     

Dynamic structural change of a twisted hexaporphyrin complex by highly specific molecular recognition

The highly specific molecular recognition of a twisted hexaporphyrin complex, tris[5,5'-bis[5,10,15-tris[methoxy(ethoxy)(2)carbonylethyl]porphyrinatozinc(II)]-2,2'-bipyridine]ruthenium(II) chloride (2), is described. Complex 2 has two trisporphyrin binding sites and can bind two triamines, tris(2-aminoethyl)amine (3) (K(1) = 3.0 x 10(8) M(-1), K(2) = 3.0 x 10(7) M(-1)), 1,1,1-tris(aminomethyl)ethane (4) (K(1) = 2.0 x 10(7) M(-1), K(2) = 1.4 x 10(6) M(-1)), tris(3-aminopropyl)amine (5) (K(1) = 3.5 x 10(6) M(-1), K(2) = 6.0 x 10(6) M(-1)), and 1,3,5-tris(aminomethyl)benzene (6) (K(1) = 2.9 x 10(6) M(-1), K(2) = 1.2 x 10(6) M(-1)), strongly with its torsional motion. The 1:2 complex between 2 and the best fit triamine 3 showed the nature of the specific rigid structure in the UV-vis, fluorescence, and (1)H NMR spectra and isothermal titration calorimetry (ITC) measurements.