Cysteine carboxyl O-methylation of human placental 23 kDa protein

C-Terminal carboxyl methylation of a human placental 23 kDa protein catalyzed by membrane-associated methyltransferase has been investigated. The 23 kDa protein substrate methylated was partially purified by DEAE-Sephacel, hydroxyapatite and Sephadex G-100 gel filtration chromatographies. The substrate protein was eluted on Sephadex G-100 gel filtration chromatography as a protein of about 29 kDa. In the absence of Mg2+, the methylation was stimulated by guanine nucleotides (GTP, GDP and GTPgammaS), but in the presence of Mg2+, only GTPgammaS stimulated the methylation which was similar to the effect on the G25K/rhoGDI complex. AFC, an inhibitor of C-terminal carboxyl methylation, inhibited the methylation of human placental 23 kDa protein. These results suggests that the substrate is a small G protein different from the G25K and is methylated on C-terminal isoprenylated cysteine residue. This was also confirmed by vapor phase analysis. The methylated substrate protein was redistributed to membrane after in vitro methylation, suggesting that the methylation of this protein is important for the redistribution of the 23 kDa small G protein for its putative role in intracellular signaling.     

Stereochemistry and dynamic behavior of some synthetic “angular” profisetinidin tetraflavanoid derivatives

The structure and stereochemistry of four synthetic “angular” tetraflavanoid-condensed tannin derivatives are examined by high-resolution variable temperature ¹H NMR. spectroscopy, and hence correlated with their dynamic behavior. Three “angular” oligomers exist as stable rotational isomers at ambient temperatures, thus contrasting with the mobility about their interflavanoid bonds of most natural profisetinidin “trimeric” and “tetrameric” homologs. A “linear” tetraflavanoid analog results from one of these regioselectively controlled condensations.     

Identification of new urinary metabolites of trimeprazine in rats by gas chromatography-mass spectrometry.

The metabolites of trimeprazine were identified in urine of rats by gas chromatography-mass spectrometry. After the oral administration of trimeprazine, the urinary metabolites were extracted with diethyl ether before or after hydrolysis with beta-glucuronidase. The identified metabolites were N-demethyltrimeprazine,3-hydroxytrimeprazine,N-demethyl-3-++ +hydroxytrimeprazine and trimeprazine sulphoxide.     

Effect of the nature of the metal oxide on selective transformation of methane under unsteady conditions in the absence of oxidant in the gaseous phase

The catalytic transformation of methane into higher hydrocarbons was studied under unsteady conditions on oxides of various metals (Pb, Fe, Nb, Ti, Cd, Mo, Mg, Zn, Zr, Bi, Mn), and also on Sr-, La-, Y-, and Mn-containing oxides of perovskite structure. It is shown that the effectiveness of the catalysts not only depends on their chemical composition, but also is determined to a considerable degree by the specific surface of the oxides. L. V. Pisarzhevskii Institute of Physical Chemistry, Academy of Sciences of Ukraine, 252039 Kiev, Prosp. Nauki, 31, Ukraine. Translated from Teoreticheskaya i éksperimental’naya Khimiya, Vol. 33, No. 2, pp. 91–95, March–April, 1997.     

Microwave-assisted solid-phase synthesis of pseudopeptides containing reduced amide bond

Procedures were developed for reducing the reaction time and improving the yield of reductive alkylation in solid phase pseudopeptide synthesis by utilizing microwave irradiation. We chose dipeptides containing the reduced amide bond ψ[CH₂NH] as a model system and optimized the microwave assisted reductive alkylation reaction in solid phase pseudopeptide synthesis using Fmoc chemistry. Under the optimized condition, the reductive alkylation reaction used for incorporating the reduced amide bond into the dipeptides was completed in only 8.5 min, whereas the normal reductive alkylation reaction required a total of 300 min. The purity and yield of the various dipeptides containing the reduced amide bond synthesized in this way are better than those achieved using the reductive alkylation method without microwave irradiation. We chose α helical peptides, which are known as a difficult sequence to synthesize, and incorporated the reduced amide bond by the microwave-assisted reductive alkylation reaction. We successfully synthesized pseudopeptides containing the reduced amide bond as a major product by using the novel microwave-assisted method, whereas the same products were obtained as a minor product when using the reductive alkylation method without microwave irradiation.     

The chemical behaviour of cobalt-stabilized carbenes having a trisubstituted silyl or germyl ligand. Stereospecific formation of benzoylsilanes from the reaction of organosilyl-cobalt tetracarbonyl derivatives with phenyllithium

We report the chemical behavior of cobalt-stabilized carbenes, R₃M(CO)₃CoC(OEt)R′, and their parent anions, R₃M(CO)₃CoC(O^?)R′, where M = Si or Ge. The anions where M = Si, R′ = Ph decompose thermally into the corresponding benzoylsilanes; when the silicon atom is chiral (R₃ = MePh-1-Np) optically active R₃SiCOPh is obtained with complete retention of configuration.     

Structure and dynamics of metallomacrocycles: recognition of zinc xylyl-bicyclam by an HIV coreceptor

As platforms for the design of metal-based therapeutic and diagnostic agents, macrocycles are rigid enough to provide strong metal binding sites and orient functional groups stereoselectively, yet flexible enough to accommodate structural changes required for induced-fit recognition of biological targets. We consider the recognition of the Zn(II) complex of the bis-tetraazamacrocycle xylyl-bicyclam, a potent anti-HIV agent, by the coreceptor CXCR4, a G-protein-coupled receptor used by HIV for membrane fusion and cell entry. NMR studies show that the macrocycles of Zn(II)(2)-xylyl-bicyclam perchlorate exist in aqueous solution as two major configurations, trans-I (nitrogen chirality R,S,R,S), and trans-III (S,S,R,R). Acetate addition induced a major structural change. X-ray crystallography shows that the acetate complex contains the unusual cis-V cyclam configuration (R,R,R,R and folded) with bidentate coordination of acetate to Zn(II) plus second-coordination-sphere double H-bond formation between diagonal NH protons on the opposite cyclam face and acetate carboxylate oxygens. Detailed 1D and 2D NMR studies show that the major configuration of Zn(II)(2)-xylyl-bicyclam acetate in aqueous solution is cis-V/trans-I. Molecular modeling shows that an analogous cis-V site can be formed when Zn(II)(2)-xylyl-bicyclam binds to CXCR4, involving the carboxylate groups of Asp262 (Zn(II) coordination) and Glu288 (double H-bonding). The second cyclam can adopt the trans-I (or trans-III) configuration with Zn(II) binding to Asp171. These interactions are consistent with the known structure-activity relationships for bicyclam anti-HIV activity and receptor mutation. Consideration of the anti-HIV activity of xylyl-bicyclam complexes of other metal ions suggests that affinity for carboxylates, configurational flexibility, and kinetic factors may all play roles in receptor recognition. For example, Pd(II) cyclam complexes interact only weakly with axial ligands and are inflexible and inactive, whereas Co(III) cyclams bind carboxylates strongly, are configurationally flexible, and yet have low activity. Our findings should aid the design of new generations of active macrocycles including highly specific chemokine receptor antagonists.     

XPS analysis of the effect of Pt addition to Pd catalysts for complete benzene oxidation

Pt-Pd bimetallic catalysts were prepared in order to develop and investigate catalysts having excellent activity and stability for benzene destruction. The effect of Pt addition to Pd catalysts is studied by XPS analysis. This revised version was published online in August 2006 with corrections to the Cover Date.     

Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cells

The pyridinium bisretinoid A2E, an autofluorescent pigment that accumulates in retinal pigment epithelial cells with age and in some retinal disorders, can mediate a detergent-like perturbation of cell membranes and light-induced damage to the cell. The photodynamic events initiated by the sensitization of A2E include the generation of singlet oxygen and the oxidation of A2E at carbon-carbon double bonds. To assess the ability of plant-derived anthocyanins to modulate adverse effects of A2E accumulation on retinal pigment epithelium (RPE) cells, these flavylium salts were isolated from extracts of bilberry. Nine anthocyanin fractions reflecting monoglycosides of delphinidin, cyanidin, petunidin and malvidin were obtained and all were shown to suppress the photooxidation of A2E at least in part by quenching singlet oxygen. The anthocyanins tested exhibited antioxidant activity of variable efficiency. The structural characteristics relevant to this variability likely included the ability to form a stable quinonoidal anhydro base at neutral pH, a conjugated diene structure in the C (pyrane) ring, the presence of hydroxyl groups on the B (benzene) ring and the relative hydrophobicity conferred by the arrangement of substituents on the B ring. Cells that had taken up anthocyanins also exhibited a resistance to the membrane permeabilization that occurs as a result of the detergent-like action of A2E.     

Solid-Phase Synthesis of Phenylacetylene Oligomers Utilizing a Novel 3-Propyl-3-(benzyl-supported) Triazene Linkage

Sequence-specific phenylacetylene oligomers consisting of functionalized monomers (hexyl benzoate, hexyl phenyl ether, benzonitrile, and tert-butylphenyl) are synthesized in gram quantities using solid-phase methods. Growing oligomers are attached to a divinylbenzene cross-linked polystyrene support by the 1-aryl-3-propyl-3-(benzyl-supported) triazene moiety. This linkage is obtained by reaction of arenediazonium tetrafluoroborate salts with a n-propylamino-modified Merrifield resin. Condensation strategies are described, producing oligomers with higher yields and simplified procedures compared to solution-phase methods. Terminal acetylene is protected with a trimethylsilyl group. After deprotection of the resin-bound terminal acetylene, an aryl iodide monomer or an aryl iodide-terminated oligomer is coupled to the supported oligomer using a palladium(0) catalyst. The cycle can be repeated to produce sequence-specific oligomers of varying length and functionality. The resulting oligomers are liberated from the polymer support by cleavage of the 1-aryl-3-propyl-3-(benzyl-supported) triazene group by reaction with iodomethane producing an aryl iodide.