Layer-by-layer assembled multilayers using catalase-encapsulated gold nanoparticles.

We introduce a novel and versatile approach for the preparation of multilayers, based on catalase-encapsulated gold nanoparticles (CAT-Au(NP)), allowing electrostatic charge reversal and structural transformation through pH adjustment. CAT-Au(NP), which are synthesized directly from CAT stabilizer, can be electrostatically assembled with anionic and cationic PEs as a result of the charge reversal of the catalase stabilizers through pH control. In particular, at pH 5.2, near the pI of catalase, dispersed CAT-Au(NP) are structurally transformed into colloidal or network CAT-Au(NP) nanocomposites. Furthermore, we demonstrate that the layer-by-layer assembled multilayers composed of PEs and CAT-Au(NP) induce an effective electron transfer between CAT and the electrode as well as a high loading of CAT and Au(NP), and resultantly exhibit a highly catalytic activity toward H(2)O(2).

Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry.

KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release a broad range of bioactive cytokines. In an effort to understand the structure-activity relationships, we have carried out syntheses of 26 new KRN7000 analogues incorporating aromatic residues in either or both side chains. Structural variations of the phytosphingosine moiety also include varying stereochemistry at C3 and C4, and 4-deoxy and 3,4-dideoxy versions. Their biological activities are described.

Stabilization of polymer-hydrogel capsules via thiol-disulfide exchange.

Polymer hydrogels are used in diverse biomedical applications including drug delivery and tissue engineering. Among different chemical linkages, the natural and reversible thiol-disulfide interconversion is extensively explored to stabilize hydrogels. The creation of macro-, micro-, and nanoscale disulfide-stabilized hydrogels commonly relies on the use of oxidizing agents that may have a detrimental effect on encapsulated cargo. Herein an oxidization-free approach to create disulfide-stabilized polymer hydrogels via a thiol-disulfide exchange reaction is reported. In particular, thiolated poly(methacrylic acid) is used and the conditions of polymer crosslinking in solution and on colloidal porous and solid microparticles are established. In the latter case, removal of the core particles yields stable, hollow, disulfide-crosslinked hydrogel capsules. Further, a procedure is developed to achieve efficient disulfide crosslinking of multilayered polymer films to obtain stable, liposome-loaded polymer-hydrogel capsules that contain functional enzymatic cargo within the liposomal subcompartments. This approach is envisaged to facilitate the development of biomedical applications of hydrogels, specifically those including fragile cargo.

Evaluation of synthetic sphingolipid analogs as ligands for peroxisome proliferator-activated receptors.

In this Letter, we assessed newly synthesized sphingolipid analogs as ligands for peroxisome proliferator-activated receptor (PPAR)alpha, PPARbeta or PPARgamma, using a dual-luciferase reporter system. We tested 640 sphingolipid analogs for ligand activity. As a result, seven types: A9, B9, C9, C50, F66, G66 and H66, were found to show agonistic activities for PPARs.

Synthesis of all stereoisomers of KRN7000, the CD1d-binding NKT cell ligand.

KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release Th1 and Th2 cytokines. In an effort to understand the structure-activity relationships, we have carried out the synthesis of a complete set of the eight KRN7000 stereoisomers, and their biological activities have been examined.

Divergent syntheses of all stereoisomers of phytosphingosine and their use in the construction of a ceramide library.

Sphingolipids such as ceramide and sphingosine-1-phosphate have recently attracted intense research interests because of their functional roles as signaling molecules in many important physiological processes, such as growth arrest, apoptosis, and inflammatory responses, and cell proliferation, vascular maturation and trafficking of lymphocytes. The well-defined modular structures of ceramides and related glycosylceramides are ideally amenable to library formation for medicinal chemistry investigation. We have developed divergent synthetic routes to all eight phytosphingosine stereoisomers and then proceeded to prepare phytosphingosine-based ceramide library composed of more than 500 compounds.

Layer-by-layer assembled charge-trap memory devices with adjustable electronic properties.

We describe a versatile approach for preparing flash memory devices composed of polyelectrolyte/gold nanoparticle multilayer films. Anionic gold nanoparticles were used as the charge storage elements, and poly(allylamine)/poly(styrenesulfonate) multilayers deposited onto hafnium oxide (HfO2)-coated silicon substrates formed the insulating layers. The top contact was formed by depositing HfO2 and platinum. In this study, we investigated the effect of increasing the number of polyelectrolyte and gold nanoparticle layers on memory performance, including the size of the memory window (the critical voltage difference between the 'programmed' and 'erased' states of the devices) and programming speed. We observed a maximum memory window of about 1.8 V, with a stored electron density of 4.2 x 1012 cm-2 in the gold nanoparticle layers, when the devices consist of three polyelectrolyte/gold nanoparticle layers. The reported approach offers new opportunities to prepare nanostructured polyelectrolyte/gold nanoparticle-based memory devices with tailored performance.

Structure-activity relationships of dimethylsphingosine (DMS) derivatives and their effects on intracellular pH and Ca2+ in the U937 monocyte cell line.

We recently reported that dimethylsphingosine (DMS), a metabolite of sphingolipids, increased intracellular pH and Ca2+ concentration in U937 human monocytes. In the present study, we found that dimethylphytosphingosine (DMPH) induced the above responses more robustly than DMS. However, phytosphingosine, monomethylphytosphingosine or trimethylsphingosine showed little or no activity. Synthetic C3 deoxy analogues of sphingosine did show similar activities, with the C16 analogue more so than C18. The following structure-activity relationships were observed between DMS derivatives and the intracellular pH and Ca2+ concentrations in U937 monocytes; 1) dimethyl modification is important for the DMS-induced increase of intracellular pH and Ca2+, 2) the addition of an OH group on C4 enhances both activities, 3) the deletion of the OH group on C3 has a negligible effect on the activities, and 4) C16 appears to be more effective than C18. We also found that W-7, a calmodulin inhibitor, blocked the DMS-induced pH increase, whereas, KN-62, ML9, and MMPX, specific inhibitors for calmodulin-dependent kinase II, myosin light chain kinase, and Ca(2+)-calmodulin-dependent phosphodiesterase, respectively, did not affect DMS-induced increases of pH in the U937 monocytes.

Syntheses of sphingosine-1-phosphate analogues and their interaction with EDG/S1P receptors.

Sphingosine-1-phosphate (S1P) is an important regulator of a wide variety of biological processes acting as an endogenous ligand to EDG/S1P receptors. In an effort to establish structure-activity relationship between EDG/S1P and ligands, we report herein homology modeling study of EDG-1/S1P(1), syntheses of S1P analogues, and cell based binding affinity study for EDG/S1P receptors.