Alkyl Tail (alkyl + tail)

Distribution by Scientific Domains

Selected Abstracts

Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimics

FEBS JOURNAL, Issue 9 2000
Kaoru Kuwabara
Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and ,,,-unsaturated ,-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two ,-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a ,-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the ,,,-unsaturated ,-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules. [source]

Enhancement of bound-state residual dipolar couplings: Conformational analysis of lactose bound to Galectin-3

Tiandi Zhuang
Abstract Residual dipolar couplings (RDCs) have proven to be a valuable NMR tool that can provide long-range constraints for molecular structure determination. The constraints are orientational in nature and are, thus, highly complementary to conventional distance constraints from NOE data. This complementarity would seem to extend to the study of the geometry of ligands bound to proteins. However, unlike transferred NOEs, where collection, even with a large excess of free ligand, results in measurements dominated by bound contributions, RDCs of exchanging ligands can be dominated by free-state contributions. Here we present a strategy for enhancement of RDCs from bound states that is based on specifically enhancing the alignment of the protein to which a ligand will bind. The protein is modified by addition of a hydrophobic alkyl tail that anchors it to the bicelles that are a part of the ordering medium needed for RDC measurement. As an illustration, we have added a propyl chain to the C terminus of the carbohydrate recognition domain of the protein, Galectin-3, and report enhanced RDCs that prove consistent with known bound-ligand geometries for this protein. [source]

Catalysis of a Peptidic Micellar Assembly Covalently Immobilized within Mesoporous Silica Channels: Importance of Amphiphilic Spatial Design

Wataru Otani
Abstract A mesostructured silica/organic composite 1-MS, constructed from a rodlike micelle of amino acid amphiphile 1 that has a condensable head group and that can be used as a template, was found to be able to catalyze the acetalization of cyclohexanone, in ethanol at 25,C (50,% in 12,h), whereas no reaction took place with unfunctionalized mesoporous silica. In sharp contrast, hydrolytic removal of the C16 alkyl tail of immobilized 1 resulted in the complete disappearance of the catalytic activity, which suggests the importance of a hydrophobic inner domain for the admission of cyclohexanone. Unsupported peptide amphiphile 2, under identical conditions to those above, was inefficient for acetalization regardless of the absence (2,% in 24,h) or presence of mesoporous silica (7,% in 24,h). Reference composite 2-MS, which is a noncovalently immobilized peptidic micelle, was virtually inactive (1,% in 24,h). These observations indicate the importance of covalent immobilization of the peptidic rod micelle for catalysis. Mesostructured silicate 3-MS hybridized with a nonpeptidic, ammonium ion amphiphile (3) showed a certain catalytic activity, but the yield (12,% in 24,h) of the acetal was much lower than that achieved by using 1-MS as the catalyst. Amorphous silica with immobilized 1 on its surface was much less active than 1-MS for acetalization (5,% in 24,h). [source]

Organoclay Nanocomposites from Ethylene,Acrylic Acid Copolymers

Sara Filippi
Abstract Summary: A study of the structure,property relationships for nanocomposites prepared by melt compounding from ethylene,acrylic acid copolymers of varied composition and molecular architecture, and organoclays modified with different ammonium ions has been made by DSC, POM, SEM, TEM, WAXD, and rheological and mechanical tests. Within the series of clays investigated, the best levels of dispersion were displayed by those organically modified with quaternary ammonium ions containing two long alkyl tails. The relevant nanocomposites were shown to possess mixed exfoliated and intercalated morphology. The spacing of the intercalated clay stacks, most of which comprise few silicate layers, was found to be independent of clay loading, in the range of 2,50 phr, and to change with the molecular architecture of the matrix polymer. An indication that the excess surfactant present in some of the clays, and the organic material added in others to expand the interlayer spacing, were expelled from the clay galleries during melt blending and acted as plasticisers for the matrix polymer, was obtained from WAXD and rheological characterisations. TEM micrograph of the nanocomposite of EAA1 with 11 phr of 15A. [source]

Synthesis and SFM Study of Comb-Like Poly(4-vinylpyridinium) Salts and Their Complexes with Surfactants

Marat O. Gallyamov
Abstract Summary: Poly(4-vinylpyridinium) bromides containing octyl and dodecyl pendant groups were synthesized. Bromide anions in these polymer salts were substituted with dodecylsulfate and bis(2-ethylhexylsuccinate) anions using ion-exchange reactions. Initially, P4VP and its derivatives loaded with hydrophobic groups were deposited on a mica surface from diluted solutions in chloroform for visualization. Images of single adsorbed macromolecules were obtained using scanning force microscopy. Original P4VP chains form partially compacted self-intersecting coils. Loading the polymer chains with large hydrophobic groups and especially the increase in the number of alkyl tails (see Figure) per monomer unit of the polymer chain leads to the stretching of the coils, and the comb-like macromolecules adopt more and more extended self-avoiding 2D conformations when deposited on the substrate. Polymer chains with large hydrophobic groups and increasing number of alkyl tails per monomer unit of the polymer chain. [source]