Human apolipoprotein (apo)E4 binds preferentially to very low density lipoproteins (VLDL) whereas apoE3 binds preferentially to high density lipoprotein (HDL), resulting in different plasma cholesterol levels with the two isoforms. To understand the molecular basis for this effect, the isolated apoE N-terminal domain (residues 1-191) and C-terminal domain (residues 192-299) together with a series of variants containing deletions in the C-terminal domain were engineered and assessed for their lipid and lipoprotein binding properties. Both isoforms can bind to a phospholipid (PL)-stabilized triolein emulsion and residues 261-299 are primarily responsible for this activity. ApoE4 exhibits greater lipid binding ability than apoE3 as a consequence of a rearrangement involving the segment spanning residues 261-272 in the C-terminal domain. The high lipid binding ability of apoE4 coupled with the VLDL particle surface being ~60% PLcovered is the basis for its preference to bind to VLDL rather than HDL. ApoE4 binds much more than apoE3 to VLDL but less than apoE3 to HDL 3 , consistent with apoE-lipid interactions being relatively unimportant for binding to HDL. The preference of apoE3 for binding to HDL 3 arises because binding is mediated primarily by interaction of the N-terminal helix bundle domain with the resident apolipoproteins which cover ~80% of the HDL 3 particle surface. Thus, the selectivity in apoE3 and apoE4 binding to HDL 3 and VLDL is dependent upon two factors. 1) The greater lipid binding ability of apoE4 relative to apoE3. 2) The differences in the nature of the surfaces of VLDL and HDL 3 particles, with the former being largely covered with PL and the latter with protein.Apolipoprotein E (apoE) regulates lipid transport and cholesterol homeostasis in the cardiovascular and central nervous systems (1-2) and is therefore a protein of major biological and clinical importance. In particular, there is great interest in understanding the structure-function relationships of apoE because of its pronounced anti-atherogenic properties (3). A complication in understanding the structure-function relationships of human apoE is the occurrence of three major isoforms (apoE2, apoE3 and apoE4), each differing by a single amino acid substitution (4). ApoE3, the most common isoform, contain cysteine at position 112 and arginine at position 158 whereas apoE2 and apoE4 contain cysteine and arginine, respectively, at both sites. ApoE2 displays defective binding to the low density lipoprotein (LDL) receptor and is associated with Type III hyperlipoproteinemia * To whom correspondence should be addressed: Dr. Sissel Lund-Katz, Children's Hospital of Philadelphia Research Institute, 3615 Civic Center Boulevard, Suite 1102 ARC, Philadelphia, PA 19104-4318, Tel: (215) FAX: (215) (5). ApoE3 and apoE4 are also associated with different lipoprotein profiles; the presence of the latter isoform leads to higher plasma cholesterol levels and an increased risk of cardiovascular disease relative to individuals with apoE3...

Thei ron(III) chloride-catalyzedF riedel-Crafts arylation of 4-aryl-4-methoxy-2,5-cyclohexadienones,w hich were easily preparedb yt he phenyliodine(III) diacetate (PIDA)-mediated oxidation of 4-arylphenols in methanol, proceededs ite-selectively to form meta-terphenyl( 2,4-diarylphenol) derivatives in good yields.T he subsequent PIDAmediated oxidation and iron(III) chloride-catalyzed Friedel-Crafts arylation of the resulting products gave the corresponding 2,4,6-triarylphenol derivatives.T he present method providesu seful highly substituted polyarylated compounds.

Disiloxanes possessing a silicon-oxygen linkage are important as frameworks for functional materials and coupling partners for Hiyama-type cross coupling. We found that disiloxanes were effectively constructed of hydrosilanes catalyzed by gold on carbon in water as the solvent and oxidant in association with the emission of hydrogen gas at room temperature. The present oxidation could proceed via various reaction pathways, such as the hydration of hydrosilane into silanol, dehydrogenative coupling of hydrosilane into disilane, and the subsequent corresponding reactions to disiloxane. Additionally, the platinum on carbon catalyzed hydrogen-deuterium exchange reaction of arylhydrosilanes as substrates in heavy water proceeded on the aromatic nuclei at 80 °C with high deuterium efficiency and high regioselectivity at the only meta and para positions of the aromatic-silicon bond to give the deuterium-labeled disiloxanes.

The atom transfer radical addition of polyhaloalkanes, such as bromotrichloromethane and polyfluoroalkyl iodine, to olefins smoothly proceeds in the presence of sodium acetate as an efficient auxiliary agent in dimethoxyethane. The present transition metal-and peroxide-free methodology is applicable to a broad scope of substrates.

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