71 research outputs found

    Lessons from Nature

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    Terrestrial and marine animals, plants, insects, and microorganisms produce a large variety of compounds for the organism's development, daily survival, self-defence, symbiosis, sexual attraction, etc. Certain of these compounds are discussed here, with emphasis not only on their isolation and structure determination, but also on the question as to why they are active. This requires a multidisciplinary approach, for a better understanding of life's processes and nature's mysteries

    V3 Tip-Dependent Species Specificity of HIV-1 Env

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    Molecular interactions of the variable envelope gp120 subunit of HIV-1 with two cellular receptors are the first step of viral infection, thereby playing pivotal roles in determining viral infectivity and cell tropism. However, the underlying regulatory mechanisms for interactions under gp120 spontaneous variations largely remain unknown. Here, we show an allosteric mechanism in which a single gp120 mutation remotely controls the ternary interactions between gp120 and its receptors for the switch of viral cell tropism. Virological analyses showed that a G310R substitution at the tip of the gp120 V3 loop selectively abolished the viral replication ability in human cells, despite evoking enhancement of viral replication in macaque cells. Molecular dynamics (MD) simulations predicted that the G310R substitution at a site away from the CD4 interaction site selectively impeded the binding ability of gp120 to human CD4. Consistently, virions with the G310R substitution exhibited a reduced binding ability to human lymphocyte cells. Furthermore, the G310R substitution influenced the gp120-CCR5 interaction in a CCR5-type dependent manner as assessed by MD simulations and an infectivity assay using exogenously expressed CCR5s. Interestingly, an I198M mutation in human CCR5 restored the infectivity of the G310R virus in human cells. Finally, MD simulation predicted amino acid interplays that physically connect the V3 loop and gp120 elements for the CD4 and CCR5 interactions. Collectively, these results suggest that the V3 loop tip is a cis-allosteric regulator that remotely controls intra- and intermolecular interactions of HIV-1 gp120 for balancing ternary interactions with CD4 and CCR5

    Configurational Assignment of Brassinosteroid Sidechain by Exciton Coupled Circular Diehroic Spectroscopy

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    Abstract: A microscale method was developed to determine the sidechain configuration of brassinosteroids, a class of potent plant growth promoters. Microscale naphthoylation followed by circular dichroie (CD) spectroscopy measurement in acetonitrile unambiguously differentiate between the two possible vieinal syn-diol configurations, (22R,23R) and (22S,23S). © 1997 Elsevier Science Ltd. Brassinosteroids are a new group of phytohormones with high growth stimulating and anti-stress activities, and which exist in only minuscule amounts. 1-3 After the isolation and characterization of brassinolide in 19794 about 40 members have been discovered in a broad spectrum of monocots and dicots as well as in gymnosperms, thus suggesting their ubiquitous occurrence in plants. 5 Structurally most brassinosteroids are AIB-trans fused steroids with 20t,3ot-diol functionalities, where ring B is 6a-oxa-6-oxo-, 6-oxo-or 6-deoxo. A characteristic feature for all native members found so far is the (22R,23R) vicinal diol in the side chain. Hydroxylation of suitable A22-unsaturated sterol precursors with OsO4 represents a key step in the synthesis of brassinosteroids, which are necessary for structural characterization of new brassinosteroids and for practical applications. Although usage of chiral ligands leads to a higher stereoselectivity of the desired native (22R,23R)-diol, 6 the (22S,23S)-isomer with lower bioactivity 7 is also formed in these reactions. 8 However, since there exists no general method for configurational assignments, a versatile and rapid analytical method based on exciton coupled circular dichroism (ECCD) of their pemaphthoates is reported here. ECCD method is a microscale procedure for determining the absolute configurations and conformations of compounds containing two or more chromophores in solution. 9,10 Hydroxyl and amino groups are converted into para-substituted benzoates, naphthoates, and other chromophores. Provided the chromophores are close-by in space, the electric transition moments will couple and give rise to a bisignate CD. A positive absolute twist between the electron transition moments of the coupled chromophores, i.e., positive chirality, will give rise to a split CD curve with positive first and negative second Cotton effects at longer and shorter wavelength, respectively. The amplitude (A-value) of the split CD, defined as the difference between AEl(first Cotton effect, longer wavelength) and Ae2(second Cotton effect, shorter wavelength), is inversely proportional to the distance between the two chromophores. 9 Importantly, in case of three or more identical 11,12 or different chromophores,13,14 the exciton split CD curve can be approximated by pair-wise addition of the interacting 1196

    Solar Water Splitting with a Hydrogenase Integrated in Photoelectrochemical Tandem Cells

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    Hydrogenases (H2ases) are benchmark electrocatalysts for H2 production, both in biology and (photo)catalysis in vitro. We report the tailoring of a p-type Si photocathode for optimal loading and wiring of H2ase through the introduction of a hierarchical inverse opal (IO) TiO2 interlayer. This proton-reducing Si j IO-TiO2 j H2ase photocathode is capable of driving overall water splitting in combination with a photoanode. We demonstrate unassisted (bias-free) water splitting by wiring Si j IO-TiO2 j H2ase to a modified BiVO4 photoanode in a photoelectrochemical (PEC) cell during several hours of irradiation. Connecting the Si j IO-TiO2 j H2ase to a photosystem II (PSII) photoanode provides proof of concept for an engineered Z-scheme that replaces the non-complementary, natural light absorber photosystem I with a complementary abiotic silicon photocathode

    Exciton coupled circular dichroic studies of self-assembled brevetoxin-porphyrin conjugates in lipid bilayers and polar solvents

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    Background: Brevetoxins, involved in the ‘red tide' as well as shellfish poisoning, are known to bind to cell membranes and membrane proteins. Brevetoxin B (BTX-B) interacts specifically with neuronal sodium channels. We recently found that BTX also induces selective ion movements across lipid bilayers through transmembrane BTX self-assemblies.Results: We examined the self-assembly of several BTX derivatives in the presence and absence of cations and lipid bilayers using the powerful porphyrin chromophores as circular dichroism labels. BTX derivatives self-assemble into tubes, which can bind to metals both when soluble and when inserted into the bilayer to form transmembrane pores. Depending on the tendency of the BTX derivative to self-aggregate (the critical “micelle” concentration, cmc), it may aggregate in solution before membrane insertion, or may insert itself into the membrane as a monomer before assembling the pore.Conclusions: The active BTX-B complex in lipid bilayers is a cyclic, transmembrane self-assembly consisting of antiparallel aligned BTX molecules that can mediate selective ion movement through membranes. The differences in pore formation mechanisms between BTX derivatives may be reflected in differences in pore formation by natural BTX variants, perhaps explaining their varying levels of toxicity

    Intramolecular Porphyrin π,π-Stacking: Absolute Configurational Assignment of Acyclic Compounds with Single Chiral Centers by Exciton Coupled Circular Dichroism

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    We report a new concept based on exciton coupled circular dichroism (CD) for assigning absolute configurations to a single chiral center *CXYSL, where X is -OH or -NH2, Y is an acyclic chain with terminal OH or -NH2, and S (small) and L (large) represent sterically distinct groups. It consists of a one step attachment of porphyrins to X and Y followed by CD measurement. The key event is intramolecular porphyrin pi,pi-stacking, which converts the flexible, acyclic substrate into a rigid stacked conformation characterized by bisignate exciton split CD curves. Since the stacked conformer is sterically controlled by the two groups, S and L, the sign of the exciton split CD is directly governed by the spatial arrangement of these groups. This approach is applicable to various acyclic compounds with different C/C distances (1,3 approximately 1,15) between the functional groups, but not to 1,2-C/C

    A two-step chemical/chiroptical method for determining absolute configurations of α-hydroxy acids

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    A general, chemical/chiroptical approach based on the CD exciton chirality method has been developed to determine the absolute configuration of α-hydroxy acids. This approach consists of amidation of the carboxyl group with ethanolamine followed by derivatization with the hydrophobic 10,15,20-triphenylporphyrinyl-5-benzoyl chromophore to form p,p-bisporphyrin derivatives which undergo intramolecular stacking. The sign of the observed bisignate couplet resulting from this stacking (in methylcyclohexane) is dictated by the preferred lower energy conformer and reflects the absolute configuration of the stereogenic center
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