Exploring the self-assembly of glycopeptides using a diphenylalanine scaffold

Diphenylalanine, a key building block for organic nanotechnology, forms discrete, rigid and hollow nanotubes that are assembled spontaneously upon their dilution from organic phase into aqueous solution. Here we report the efficient preparation of several S-linked glycosylated diphenylalanine analogues bearing different monosaccharide, di-saccharide and sialic acid residues. The self-assembly studies revealed that these glycopeptides adopted various structures and glycosylation could be a tool to manipulate the self-assembly process. Moreover, the solubility of these analogues was found to be much greater than diphenylalanine, which could open new applications based on these nanostructures.     

A unique paradigm for a Turn-ON near-infrared cyanine-based probe: noninvasive intravital optical imaging of hydrogen peroxide

The development of highly sensitive fluorescent probes in combination with innovative optical techniques is a promising strategy for intravital noninvasive quantitative imaging. Cyanine fluorochromes belong to a superfamily of dyes that have attracted substantial attention in probe design for molecular imaging. We have developed a novel paradigm to introduce a Turn-ON mechanism in cyanine molecules, based on a distinctive change in their π-electrons system. Our new cyanine fluorochrome is synthesized through a simple two-step procedure and has an unprecedented high fluorescence quantum yield of 16% and large extinction coefficient of 52,000 M(-1)cm(-1). The synthetic strategy allows one to prepare probes for various analytes by introducing a specific triggering group on the probe molecule. The probe was equipped with a corresponding trigger and demonstrated efficient imaging of endogenous hydrogen peroxide, produced in an acute lipopolysaccharide-induced inflammation model in mice. This approach provides, for the first time, an available methodology to prepare modular molecular Turn-ON probes that can release an active cyanine fluorophore upon reaction with specific analyte.     

Nilpotency of Bocksteins, Kropholler's hierarchy and a conjecture of Moore

We show that the class of pairs (Γ,H) of a group and a finite index subgroup which verify a conjecture of Moore about projectivity of modules over ZΓ satisfy certain closure properties. We use this, together with a result of Benson and Goodearl, in order to prove that Moore's conjecture is valid for groups which belongs to Kropholler's hierarchy LHF. For finite groups, Moore's conjecture is a consequence of a theorem of Serre, about the vanishing of a certain product in the cohomology ring (the Bockstein elements). Using our result, we construct examples of pairs (Γ,H) which satisfy the conjecture without satisfying the analog of Serre's theorem.     

Quantized pumping and topology of the phase diagram for a system of interacting bosons

Interacting lattice bosons at integer filling can support two distinct insulating phases, which are separated by a critical point: the Mott insulator and the Haldane insulator [E.?G. Dalla Torre, E. Berg, and E. Altman, Phys. Rev. Lett. 97, 260401 (2006).]. The critical point can be gapped out by breaking lattice inversion symmetry. Here, we show that encircling this critical point adiabatically pumps one boson across the system. When multiple chains are coupled, the two insulating phases are no longer sharply distinct, but the pumping property survives. This leads to strict constraints on the topology of the phase diagram of systems of quasi-one-dimensional interacting bosons.     

Modelling Photosynthesis with ZnII-Protoporphyrin All-DNA G-Quadruplex/Aptamer Scaffolds

All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of Zn^II-protoporphyrin IX (Zn^IIPPIX)-functionalized G-quadruplex conjugated to the 3′- or 5′-end of the tyrosinamide (TA) aptamer and Zn^IIPPIX/G-quadruplex linked to the 3′- and 5′-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from Zn^IIPPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV²⁺, bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of Zn^IIPPIX/G-quadruplex by TA-MV²⁺ controls the efficiency of the generation of TA-MV^+.. The photosystem-controlled formation of TA-MV^+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin-NADP⁺ reductase (FNR)-catalysed reduction of NADP⁺ to NADPH by TA-MV^+., and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1-phenylethanol by NADPH.     

Naphthoquinone–Dopamine Hybrids Inhibit α-Synuclein Aggregation,Disrupt Preformed Fibrils,and Attenuate Aggregate-Induced Toxicity

Accumulation and aggregation of the intrinsically disordered protein α-synuclein (α-Syn) into amyloid fibrils are hallmarks of a series of heterogeneous neurodegenerative disorders, known as synucleinopathies and most notably Parkinson's disease (PD). The crucial role of α-Syn aggregation in PD makes it an attractive target for the development of disease-modifying therapeutics that would inhibit α-Syn aggregation or disrupt its preformed fibrillar assemblies. To this end, we have designed and synthesized two naphthoquinone–dopamine-based hybrid small molecules, NQDA and Cl-NQDA, and demonstrated their ability to inhibit in vitro amyloid formation by α-Syn using ThT assay, CD, TEM, and Congo red birefringence. Moreover, these hybrid molecules efficiently disassembled preformed fibrils of α-Syn into nontoxic species, as evident from LUV leakage assay. NQDA and Cl-NQDA were found to have low cytotoxicity and they attenuated the toxicity induced by α-Syn towards SH-SY5Y neuroblastoma cells. NQDA was found to efficiently cross an in vitro human blood–brain barrier model. These naphthoquinone–dopamine based derivatives can be an attractive scaffold for therapeutic design towards PD.     

PROTECTION BY THE FLUORIDE ION AGAINST PHTHALOCYANINE-INDUCED PHOTODYNAMIC KILLING OF CHINESE HAMSTER CELLS

When a dilute F- solution was added to a culture of Chinese hamster cells that had been preincubated with an aluminium phthalocyanine sensitizer derived from AlPcCl, the photosensitivity of the cells was markedly reduced compared to control cells not treated with F-. Under the same treatment conditions, the reduction in [3H]thymidine incorporation into cellular DNA caused by light and this sensitizer and the production of DNA-protein crosslinks caused by light and this sensitizer were also inhibited by F-. In contrast, the killing of Chinese hamster cells, the reduction of thymidine incorporation by the cells, and the production of DNA-protein crosslinks in the cells caused by the combination of light and either Photofrin II or the silicon phthalocyanine HOSiPcOSi(CH3)2(CH2)3-N(CH3)2 were not inhibited by F-. We conclude that the aluminium phthalocyanine sensitizer used is largely or completely AlPc(OH)(H2O), that it is converted to a fluoro complex by F-, and that this compound probably is a less efficient generator of photochemical damage at a critical cellular target(s) than is AlPc(OH)(H2O). The inhibition of thymidine incorporation and DNA-protein crosslink formation indicates that the effects of F- can be expressed at intracellular sites. It is further concluded that the silicon phthalocyanine sensitizer and Photofrin II do not interact significantly with F-.     

Pattern formation on anisotropic and heterogeneous catalytic surfaces

We review experimental and theoretical work addressing pattern formation on anisotropic and heterogeneous catalytic surfaces. These systems are typically modeled by reaction-diffusion equations reflecting the kinetics and transport of the involved chemical species. Here, we demonstrate the influence of anisotropy and heterogeneity in a simplified model, the FitzHugh-Nagumo equations. Anisotropy causes stratification of labyrinthine patterns and spiral defect chaos in bistable media. For heterogeneous media, we study the situation where the heterogeneity appears on a length scale shorter than the typical pattern length scale. Homogenization, i.e., computation of effective medium properties, is applied to an example and illustrated with simulations in one (fronts) and two dimensions (spirals). We conclude with a discussion of open questions and promising directions that comprise the coupling of the microscopic structure of the surface to the macroscopic concentration patterns and the fabrication of nanostructures with heterogeneous surfaces as templates. (c) 2002 American Institute of Physics.     

TpPtMe(H)(2): why is there H/D scrambling of the methyl group but not methane loss?

The reactivity of TpPtMe(H)(2) (Tp = hydrido-tris(pyrazolyl)borate) was investigated. This complex is remarkably resistant to methane loss; heating it in methanol at 55 degrees C does not lead to either methane or hydrogen loss. When CD(3)OD is used, reversible H/D scrambling of the hydrides and the methyl hydrogens occurs. This reactivity was investigated by density functional theory (DFT) methods at the mPW1k/LANL2DZ+P//mPW1k/LANL2DZ level. It was found that methane loss cannot occur due to the rigidity of the Tp ligand, which does not allow the trans geometry which would be required for the product of methane elimination, TpPtH. The resulting complex is very high in energy, and therefore the loss of methane is unfavorable. On the other hand, H/D scrambling of the methyl ligand is relatively facile. It proceeds through an eta(2-CH)-CH(4) complex, even though methane loss is not observed. The model system, [(NH(3))(3)PtMe(H)(2)](+) was examined to verify that the cause of the observations is the rigidity of the Tp system. The reaction was investigated at a number of levels of DFT. It was concluded that investigations of similar sized systems should be examined at the above level of theory or the mPW1k/SDB-cc-pVDZ//mPW1k/SDD level for improved accuracy of the energetic calculations.     

Cohomology of discrete groups in harmonic cochains on buildings

Modules of harmonic cochains on the Bruhat-Tits building of the projective general linear group over ap-adic field were defined by one of the authors, and were shown to represent the cohomology of Drinfel’d’sp-adic symmetric domain. Here we define certain non-trivial natural extensions of these modules and study their properties. In particular, for a quotient of Drinfel’d’s space by a discrete cocompact group, we are able to define maps between consecutive graded pieces of its de Rham cohomology, which we show to be (essentially) isomorphisms. We believe that these maps are graded versions of the Hyodo-Kato monodromy operatorN.