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Systemic change: A system of transformations between helical structures was observed to be governed by interactions mediated by the electronic effects of substituents, entropic effects, the conformational preferences of organic building blocks, and the coordinative preferences of the metal ion. All of these effects were important, but all must be considered together to allow the prediction of the product observed (see scheme).

This work introduces a biscysteine ligand to build a small peptidic model system of hydrogenase enzymes. FeC5H4CO–Cys–OMe2LH2 has been employed as a chelate for an iron–carbonyl complex, which mimics two essential structural properties of the hydrogenase class of enzymes, namely the coordination of the iron–carbonyl core to peptide ligands and the presence of an electrochemical relay in spatial proximity. The treatment of LH2with Fe3CO12yields LFe2CO63a, which is the first peptidecoordinated iron hydrogenase activesite model complex. Compound 3awas fully characterized spectroscopically 1H NMR, 13C NMR, IR and Mössbauer spectroscopy, mass spectrometry and elemental analysis. A singlecrystal Xray analysis confirms the proposed structure and reveals a staggered conformation of the Fe2CO6S2core. Fourier transform infrared FTIR spectroelectrochemistry reveals an electronic interaction between the peptide backbone and the iron–carbonyl cluster, but not with the ferrocene subsite. The introduction of this peptidic cysteinebased ligand into hydrogenase model chemistry helps to confirm the proposed cofactor biosynthesis and understand the electronic interplay between the metal–carbonyl active site and the protein environment in this important class of enzymes.© WileyVCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008

Foldamers at an angle: Metal‐directed assembly dictates the perpendicular or parallel orientation of helically folded aromatic oligoamide modules and mediates the communication of their relative handedness (see figure).

L’informatique a envahi notre société, modifié nos pratiques quotidiennes, transformé les méthodes de travail. Toute l’information produite, transmise, traitée, stockée dans ces nouvelles pratiques est sous forme numérique. Les obsolescences constantes de la technologie et l’absence d’organisations appropriées rendent cette information de plus en plus vulnérable au temps. La pérennisation de cette information pose des problèmes nouveaux à nombre d’organismes et d’entreprises. La recherche scientifique n’échappe pas à cette difficulté. Une norme fondamentale, le modèle de référence OAIS, nous permet de comprendre en profondeur le problème posé. Ce modèle constitue une base indispensable pour concevoir des solutions qui commencent à voir le jour.

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We report on the dramatic effect of increasing helix diameter on the hybridization of oligopyridine‐dicarboxamide strands into double helices. Upon replacing a single pyridine by a 1,8‐diazaanthracene unit within an oligomeric strand, a 4.7 Å enlargement of the helix diameter occurs parallel to the long anthracene axis. This structure change results in a spectacular stabilization of the double helical hybrids derived from these strands (factors of over 107). Detailed investigations of the hybridization process using X‐ray crystallography, NMR, fluorescence measurements and molecular mechanics calculations allowed us to assign the duplex stabilization to two enthalpic effects. First, the increase in diameter results in an augmented surface, involved in intermolecular π–π stacking. Second, the enlarged diameter leads to a lower tilt angle of the helical strand, with respect to the helix axis, which in turn results in smaller dihedral angles at the aryl–amide linkages and thus a considerably lowered enthalpic cost of the spring‐like extension of the strands during the hybridization process. These results provide novel insights into how subtle tuning of molecular components may result in considerable and rationalizable changes in double helical supramolecular architectures.

Three aromatic oligoamides have been prepared that have alternating 1,6‐diaminopyridine and 1,6‐pyridinedicarboxylic acid units at the center of the sequence and two 8‐amino‐2‐quinolinecarboxylic acid units at each extremity. The three oligomers differ in the number–‐3, 5, or 7—of pyridine units in the sequence. They were designed to adopt helically folded conformations in solution and in the solid state. The sequence of monomers was chosen so that the diameter of the helix is larger in the center than at each extremity, and hence they resemble helically wrapped apple peels. According to modeling studies, the pyridine units were expected to define a polar hollow within the helix that is large enough to accommodate small polar guests, whereas the quinoline units at each end of the oligomeric sequences were expected to completely cap the hollow and transform the helix cavities into a closed shell that may act as a capsule. Crystallographic studies demonstrate that the oligomers do fold into helices that define a cavity isolated from the surrounding medium in the solid state. Depending on the number of pyridine rings, one or two water molecules are bound within the capsules. The crystal structure of a capsule fragment shows that MeOH can also be hosted by the largest oligomer. Solution NMR studies confirm that binding of water also occurs in solution with the same stoichiometry as observed in the solid state. The capsules have distinct signals depending on whether they are empty, half‐full, or full, and these species are in slow exchange on the NMR timescale at low temperature. Indeed, the binding and release of water molecules requires a significant conformational distortion of the helix that slows down these processes. The addition of small polar molecules such as methanol, hydrazine, hydrogen peroxide, or formic acid to the largest capsule leads to the observation of new sets of NMR signals of the capsules that were assigned to complexes with these guests. However, water appears to be the preferred guest.

The increasing importance of hydrogenase enzymes in the new energy research field has led us to examine the structure and dynamics of potential hydrogenase mimics, based on a ferrocene–peptide scaffold, using molecular dynamics (MD) simulations. To enable this MD study, a molecular mechanics force field for ferrocene‐bearing peptides was developed and implemented in the CHARMM simulation package, thus extending the usefulness of the package into peptide–bioorganometallic chemistry. Using the automated frequency‐matching method (AFMM), optimized intramolecular force‐field parameters were generated through quantum chemical reference normal modes. The partial charges for ferrocene were derived by fitting point charges to quantum‐chemically computed electrostatic potentials. The force field was tested against experimental X‐ray crystal structures of dipeptide derivatives of ferrocene‐1,1′‐dicarboxylic acid. The calculations reproduce accurately the molecular geometries, including the characteristic C2‐symmetrical intramolecular hydrogen‐bonding pattern, that were stable over 0.1 μs MD simulations. The crystal packing properties of ferrocene‐1‐(D)alanine‐(D)proline‐1′‐(D)alanine‐(D)proline were also accurately reproduced. The lattice parameters of this crystal were conserved during a 0.1 μs MD simulation and match the experimental values almost exactly. Simulations of the peptides in dichloromethane are also in good agreement with experimental NMR and circular dichroism (CD) data in solution. The developed force field was used to perform MD simulations on novel, as yet unsynthesized peptide fragments that surround the active site of [Ni–Fe] hydrogenase. The results of this simulation lead us to propose an improved design for synthetic peptide‐based hydrogenase models. The presented MD simulation results of metallocenes thereby provide a convincing validation of our proposal to use ferrocene–peptides as minimal enzyme mimics.

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We are interested in the relation between the pathwidth of a biconnected outerplanar graph and the pathwidth of its (geometric) dual. Bodlaender and Fomin [3], after having proved that the pathwidth of every biconnected outerplanar graph is always at most twice the pathwidth of its (geometric) dual plus two, conjectured that there exists a constant csuch that the pathwidth of every biconnected outerplanar graph is at most cplus the pathwidth of its dual. They also conjectured that this was actually true with cbeing one for every biconnected planar graph. Fomin [10] proved that the second conjecture is true for all planar triangulations. First, we construct for each p≥ 1, a biconnected outerplanar graph of pathwidth 2p+ 1 whose (geometric) dual has pathwidth p+ 1, thereby disproving both conjectures. Next, we also disprove two other conjectures (one of Bodlaender and Fomin [3], implied by one of Fomin [10]. Finally we prove, in an algorithmic way, that the pathwidth of every biconnected outerplanar graph is at most twice the pathwidth of its (geometric) dual minus one. A tight interval for the studied relation is therefore obtained, and we show that all cases in the interval happen. © 2006 Wiley Periodicals, Inc. J Graph Theory 55: 27–41, 2007

The effect of breed [Creole (CR) vs. Large White (LW)] on performance and physiological responses during acclimation to high ambient temperature was studied in 2 experiments involving 24 (12/breed) growing pigs each. Pigs were exposed to 24°C for 10 d (d −10 to −1) and thereafter to a constant temperature of 31°C for 16 d (d 1 to d 16) in Exp. 1 and for 20 d (d 1 to d 20) in Exp. 2. For both experiments, the temperature change was achieved over 4 h on d 0. The first experiment began at 105 d of age, and the average BW of CR and LW pigs was 36.6 ± 2.5 kg and 51.7 ± 3.0 kg, respectively. The second experiment was designed to compare both breeds at a similar BW (about 52 kg on d 0). Pigs were individually housed and given ad libitum access to feed. At 24°C, ADG was lower (P< 0.01) in CR than in LW (602 vs. 913 g/d and 605 vs. 862 g/d in Exp. 1 and 2, respectively), but the ADFI was not affected by breed (190 and 221 g · d−1·kg−0.60in Exp. 1 and 2, respectively). Short-term thermoregulatory responses during the 4-h transition from 24 to 31°C (d 0) were analyzed according to a linear plateau model to determine the break point temperature, above which rectal temperature (RT), cutaneous temperature (CT), and respiratory rate (RR) began to change. The CT increased linearly with temperature increase (0.22°C/°C) and was less (P< 0.05) in CR than in LW (by −0.3°C on average). In both experiments, the break point temperature for RT was not affected by breed (27.6°C on average), whereas for RR it was greater (P< 0.05) in CR than in LW (27.5 vs. 25.5°C, P< 0.01). On average, ADFI declined by about 50 g · d−1· kg−0.60from d −1 to d 1 (P< 0.01), and thereafter at 31°C, it gradually increased (23 g · d−1· kg−0.60; P< 0.05), suggesting an acclimation to high exposure. This response was not influenced by breed. After the day that marked the beginning of the acclimation response (i.e., the threshold day), RR, CT, and RT declined over the duration of exposure to 31°C (P< 0.05) in both experiments. During this period, RT and CT were less in CR than in LW pigs (39.6 vs. 39.9°C and 37.9 vs. 38.2°C, respectively; P< 0.05), whereas RR was not affected by breed. The threshold day at which RT began to decline was less in CR than in LW pigs (0.18 vs. 1.17 d and 0.39 vs. 0.93 d in Exp. 1 and 2, respectively; P< 0.05). In conclusion, this study suggests that short- and long-term physiological reactions during heat acclimation differed when CR and LW pigs were compared at the same age or BW.

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Cationic gemini surfactants complexed with anionic oligoglycine-aspartate (called gemini peptides hereafter) were synthesized, and their aggregation behaviors were studied. The effects of the hydrophobic chain length (C10−C22) and the length of the oligoglycine (0−4) were investigated, and it was clearly shown by critical micellar concentration, Krafft temperature, and isothermal surface pressure measurements that the hydrophobic effect and interpeptidic interaction influence the aggregation behavior in a cooperative manner. Below their Krafft temperatures, some of them formed both hydro- and organogels with three-dimensional networks and the Fourier transform infrared measurements show the presence of interpeptidic hydrogen bonds.

The unambiguous elucidation of a new folded structure in solution may prove to be a very challenging task. The NMR protocols developed for solving the solution structures of α‐peptides have been applied to aliphatic β‐ and γ‐peptides but are not directly applicable to aromatic oligomers. In particular, the string of spin systems in an aromatic sequence cannot be reconstituted solely from correlations between protons. For aromatic oligomers, it is shown that the assignment of a large part of the 13C NMR spectrum through HMBC and HSQC experiments allows to unambiguously assign proton NMR spectra and in turn to interpret NOE correlations. This has been implemented both with quinoline‐ and pyridine‐derived oligoamide foldamers, and should be applicable to a wide range of oligomers including various combinations of monomers. The NOE correlations allow the unambiguous solution structure elucidation of helical conformations of oligoamides derived from pyridine and quinoline monomers showing that, in these series, the solution structures correspond very well to the structures observed in the solid state.

The relationship between bulk membrane fluidizing effect of ethanol and its toxicity due to oxidative stress is still unknown. To elucidate this issue, membrane fluidity of primary rat hepatocytes was studied by measuring order parameter after inhibition of ethanol-induced oxidative stress. We showed that pretreating cells with either 4-methyl-pyrazole (to inhibit ethanol metabolism), thiourea [a reactive oxygen species (ROS) scavenger], or vitamin E (a free radical chain-breaking antioxidant) prevented the ethanol-induced increase in membrane fluidity, thus suggesting that ethanol metabolism and ROS formation were involved in this elevation. The effects of membrane stabilizing agents (ursodeoxycholic acid or ganglioside GM1), shown to prevent fluidification, next pointed to a role for this increase in membrane fluidity in the development of ethanol-induced oxidative stress. Indeed, ROS production, lipid peroxidation, and cell death were all inhibited by these agents. In contrast, the fluidizing compounds Tween 20 or 2-(2-methoxyethoxy) ethyl 8-(cis-2-n-octylcyclopropyl) octanoate, which increased the membrane fluidizing effect of ethanol, enhanced the related oxidative stress. Using electron paramagnetic resonance to determine low molecular weight iron, we finally demonstrated that membrane fluidity influence proceeded through an increase in low molecular weight iron to enhance oxidative stress. In conclusion, the present findings clearly highlight the pivotal role of membrane fluidity in ethanol-induced oxidative stress and the potential therapeutic effect of membrane stabilizing compounds.

A new convergent synthetic scheme has been developed to prepare oligoamides of 2,6-diaminopyridine and 4-decyloxy-2,6-pyridinedicarboxylic acid. These compounds adopt stable single helical conformations in solution. NMR and circular dichroism studies show that intramolecular and intermolecular chiral induction of handedness in these helices is possible. Intramolecular induction is effected by attaching a single chiral group to the end of an oligomer. Intermolecular induction results from various noncovalent interactions between chiral carboxylic or sulfonic acids and the terminal residues of the oligoamides. Intramolecular induction appears to be more efficient than intermolecular induction. When both effects compete, intramolecular induction prevails. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Recent studies have demonstrated the importance of lymphocytes, especially CD4+T cells, in early lesions of atherosclerosis in hypercholesterolemic mice. However, the role of other T cell subpopulations, like CD8+T cells or TCRγδ T lymphocytes, is not yet clear. We have therefore generated apolipoprotein E-deficient mice genetically deficient in specific T lymphocyte subpopulations and measured atherosclerotic lesions in the aortic sinus and en facewhole aorta preparation at 18 weeks and at 1 year of age. Whereas TCRγδ+T lymphocytes appeared to play a modest role, TCRαβ+T lymphocytes played a major role as their deficiency significantly prevented early and late atherosclerosis at all arterial sites. However, neither CD4+nor CD8+T cells induced any significant decrease of the lesions at the aortic sinus, suggesting that compensatory proatherogenic mechanisms are operating at this site. Interestingly, the absence of CD4+T cells led to a dramatic increase in early lesion abundance at the level of the descending thoracic and abdominal aorta, which was still obvious at 1 year. In conclusion, whereas the TCRαβ+lymphocyte subset in its whole contribute to aggravate both early and late atherosclerosis, the CD4+T subpopulation appears to be critically protective at the level of the lower part of the aorta.

Can one join both ends of a helix? A helical aromatic oligoamide was macrocyclized into a saddle-shaped bifunctional clip molecule that self-assembles into discrete circular dodecamers in the solid state and shows great potential for binding aromatic acid guests in solution. The cyclization step requires that the helix is only partly denatured in the reaction medium.

Aromatic oligoamide foldamers possess a high potential for mimicking the secondary structures of biopolymers. These oligomers are efficiently designed, easy to synthesize, and allow one to reach a wide range of stable folded states. The aryl−amide bond rotation can be restricted through specific attractive and repulsive interactions between the amide and the other functional groups at the ortho position on the aryl moiety. The overall conformation of an oligomer results from the simple linear combination of the local conformational preferences at each amide bond. Thus, the curvature of the oligomeric strand may be tuned from strictly linear to highly bent, giving rise to helices of controllable diameter and extended linear conformations. Conformational rearrangements such as helical−linear strand transitions may be induced upon changing the local conformational preference of aryl−amide bonds. These oligomers also aggregate in various ways, such as stacks of discs, face-to-face hydrogen-bonded linear dimers, or entwined double helices. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Abstract: How pHichanges, more specifically alkalinization, affect the apoptotic cascade has yet to be determined. The aim of the present work was to test the involvement of mitochondria in the apoptotic cascade triggered by benzo(a)pyrene [B(a)P] and to determine the role of pHichanges and p53 relative to mitochondria. Our results indicate that B(a)P‐induced apoptosis might rely upon a p53‐dependent and a pH‐sensitive mitochondrial dysfunction.

The organization of cationic dimeric (gemini) surfactants assembled in cylindrical micelles was investigated using polarization modulation infrared linear dichroism (PM-IRLD) and molecular dynamics simulations. These molecules consist of two quaternary ammonium amphiphiles connected at the headgroup by an ethylene spacer, resulting in an elongated polar head. PM-IRLD measurements and molecular dynamics simulations indicate that the long axis of the surfactant headgroup may adopt a preferred orientation of ca. 30−50° with respect to the micelle cylinder axis. This may be interpreted as the result of the competition between the charge repulsion between headgroups which favors an orientation of the molecules perpendicular to the cylinder axis (high curvature) and the steric repulsion between hydrophobic tails which favors an orientation of the molecules parallel with the cylinder axis (flat curvature). Experiment and calculation both show a water layer a few angstroms thick with a specific orientation at the micelle interface.

Helically preorganized oligopyridine‐dicarboxamide strands are found to undergo dimerization into double helical supramolecular architectures. Dimerization of single helical strands with five or seven pyridine rings has been characterized by NMR and mass spectrometry in various solvent/temperature conditions. Solution studies and stochastic dynamic simulations consistently show an increasing duplex stability with increasing strand length. The double helical structures of three different dimers was characterized in the solid phase by X‐ray diffraction analysis. Both aromatic stacking and hydrogen bonding contribute the double helical arrangement of the oligopyridine‐dicarboxamide strand. Inter‐strand interactions involve extensive face‐to‐face overlap between aromatic rings, which is not possible in the single helical monomers. Most hydrogen bonds occur within each strand of the duplex and stabilize its helical shape. Some inter‐strand hydrogen bonds are found in the crystal structures. Dynamic studies by NMR as well as by molecular modeling computations yield structural and kinetic information on the double helices and on monomer–dimer interconversion. In addition, they reveal the presence of a spring‐like extension/compression as well as rotational displacement motions.

Molecular strands composed of alternating 2,6‐diaminopyridine and 2,6‐pyridinedicarbonyl units have been designed to self‐organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1and 20, and undecameric strand 15have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X‐ray diffraction analysis for four of these compounds. Helices from pentameric strands 12and 14extend over one turn, and helices from heptameric 20and undecameric 15species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation.

Axial metal complexation was used in the organization of the cobalt(II) meso-tetra(trimethylsilylethynyl)porphyrin, CoPTMS, by the Langmuir−Blodgett (LB) technique or by self-assembly (SA). The axial ligand is a para-substituted pyridine that carries a long aliphatic chain, C18NHPy, in the case of the LB technique or a triethoxysilane group, SiPy, in the case of SA. In both cases, monomolecular films of nonaggregated porphyrins have been obtained and characterized by IR and UV spectroscopies, linear dichroism, and X-ray diffraction. A 1/1/5 mixture of CoPTMS, C18NHPy, and methyl eicosanoate spread on a silver nitrate subphase led to the formation of a silver acetylide polychelate of porphyrins. After transfer onto a solid substrate, the macrocycles displayed a flat-on orientation. The polychelate monolayers are robust enough to allow easy dissolution of the methyl eicosanoate filling molecule without disturbing the macrocycle orientation inside the LB film.

Ruthenium phthalocyanine (RuPc) monolayers were obtained by self-assembly on pyridino-functionalized metal oxide substrates, by coordination between the ruthenium ions and the pyridino groups. The substrates were functionalized by silanization with a bifunctional silane. Soluble ruthenium phthalocyanines, axially coordinated by labile benzonitrile groups, were used. A ligand exchange reaction was involved, one benzonitrile group being replaced by pyridine. These RuPc monolayers were characterized by transmission UV−vis spectroscopy, atomic force microscopy, polarization modulation infrared reflection−absorption spectroscopy, and time-of-flight secondary ion mass spectrometry. A second ligand exchange reaction allowed us to build RuPc bilayers by two different strategies. A mixed RuPc/cobalt porphyrin bilayer was also obtained.

Dynamic combinatorial chemistry is based on the reversible combination of initial building blocks to form dynamic combinatorial libraries. It has recently emerged as an efficient strategy to detect and to evaluate affinity between the library products and a target molecule. In this review, examples from various fields of chemistry and biochemistry are presented and extensively discussed. The last section deals with the practical aspects for implementing this approach.

The synthesis, phase behavior, and mixing properties of cationic dimeric (gemini) surfactants having one or two perfluoroalkyl chains is described and compared to that of analogue hydrocarbon surfactants. The combination of the dimeric character of the amphiphiles with the high hydrophobicity of the fluorocarbon chains leads to very low critical micelle concentration values and unusually low characteristic times of exchange between surfactants in the bulk solution and surfactants in the aggregate. This results in slow exchange on the NMR time scale, which allows a practical study of micellization and comicellization by NMR. With respect to the morphology of the aggregates, the fluorocarbon amphiphiles do not simply behave as more hydrophobic amphiphiles. Instead, they assemble into various structures including very stable unilamellar and multilamellar vesicles not seen in their hydrocarbon analogues. The hybrid hydrocarbon−fluorocarbon dimeric surfactant exhibits features of both families. In particular it mixes with either hydrocarbon or fluorocarbon surfactants, whereas the latter two undergo a macroscopic phase separation.

The linear oligo‐isophthalamide strand 1undergoes a conformational reorganization upon binding of a cyanuric acid template as effector to afford a helical disklike object possessing radially disposed alkyl residues. Solvophobic and stacking interactions, in turn, drive a “second level” self‐assembly of the templated structure, the stacking of the helical disks, to yield fibers as revealed by electron microscopy. These data provide insight into the interplay of the different structural and interactional features of the molecular components towards the formation of supramolecular fibers through sequential hierarchical self‐assembly events and suggest design strategies for the effector‐controlled generation of related supramolecular assemblies.

Ruthenium phthalocyanines bearing pyridine-4-carboxaldehyde as an axial ligand were synthesized. The carboxaldehyde group of the apical ligand pointing out from the phthalocyanine ring was used to link the complex to chemically modified surfaces. The resulting monolayer was characterized by ellipsometry, IRRAS, XPS, X-ray reflectivity, and SPM. The grafting of RuPc to the surface is stable.

The phase behavior of aqueous solutions of several dissymmetric gemini surfactants (with two hydrophobic chains of different lengths) was studied. From rheological and X-ray scattering studies as well as from freeze fracture imaging, some general patterns of the phase behavior were observed which are remarkably different from those observed for monomeric surfactants. The sequence of phases observed with increasing surfactant concentration was an isotropic wormlike micellar phase, multilayered structures which are first isotropic and then organized with orientational ordering, and an inverted hexagonal phase. The multilayered phase showed a scattering peak corresponding to a periodicity of 40 Å indicating the presence of stacks of bilayers without a water layer in between. For some of the samples, cryo-TEM showed that wormlike micelles (WLM) evolve into a ribbonlike structure (elongated bilayer). Upon further increase in concentration, the ribbons transform into multilayered structures with a well-defined width.

The selection of the receptor presenting the strongest affinity for a barbiturate substrate from a dynamic combinatorial library of constituents differing in structure and conformation/configuration is described. The gradual addition of the barbiturate to an equilibrating mixture of hydrazone isomers leads to the quantitative shift towards a single species, 3, which presents highest complementarity to the substrate and yields the supramolecular entity 3:4.

The functionalized ligands 1 and 2 bearing hydrogen-bonding recognition groups have been synthesized. Their assembly by metal ions such as Cu^I and Pd^II having different coordination geometries generates different receptor architectures for the binding of suitable substrates. Addition of the complementary bis(imide) Janus molecules (4–7) to [1a, 2a, CuTf] or to [1b, 2b, Pd(BF4)2] mixtures leads to a moderate selective increase of the fraction of the [(1a)2Cu]⁺ or [(1b)2Pd]²⁺ complex depending on the Janus substrate used. Largest enhancements are observed for those Janus substrates that may be expected to display highest geometrical complementarity with the two complexes. These results represent a process directed by target binding based on dynamic combinatorial chemistry.

Self-assembled monolayers of 1,4-diisocyanobenzene on gold were used to bind ruthenium phthalocyanines to the surface by axial ligation of the macrocycle with isocyanide groups pointing out from the SAM. The 1,4-diisocyanobenzene SAM and the RuPc-1,4-diisocyanobenzene bilayer were characterized by ellipsometry, IRRAS, XPS, and SPM. The grafting of RuPc to the SAM is stable. The thickness of the film increases from 10 to 15 Å upon RuPc ligation. IRRAS reveals that both ends of the 1,4-diisocyanobenzene are affected by the N&tbd1;C to metal interaction occurring at the other end. XPS indicates that each RuPc macrocycle covers ~12 1,4-diisocyanobenzene molecules in the bilayer.

Three cDNA clones of 1.6 (3u), 1.2 (5g) and 0.6 (5b) kbp, specific for peripherin, a neuronal intermediate filament protein (IFP), have been isolated from a murine neuroblastoma cell lambda gt11 library by immunoscreening using peripherin antiserum. Antibodies eluted from the fusion proteins produced by clones 3u and 5g recognize the peripherin spots on immunoblots. Where they overlap the three cDNAs have identical sequences. cDNA 5g exhibits the closest homology to type III IFP cDNAs. cDNA 3u is identical to the corresponding region of cDNA 5g, except for the insertion of a 96 bp fragment at a position corresponding to the junction of exons 4 and 5 in type III IFP cDNAs. cDNA 5b is also identical to the corresponding region of cDNA 5g, except for the deletion of a 62 bp fragment at the junction of exons 8 and 9 in type III IFP cDNAs. S1 mapping experiments performed with probes covering the 3′ end of the two unexpected regions show that three distinct mRNAs correspond to the three cDNAs. Moreover, three peripherin products, two minor 61 and 56 kd products in addition to the major 58 kd peripherin, are observed when poly(A)+ RNA is in vitro translated, the 61 kd peripherin being translated from the 3u‐selected RNA. The three RNAs originate from alternative splicing of a unique peripherin gene, thus generating polymorphism of peripherin.

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The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A-encoded class II major histocompatibility complex antigens, which differ from those of other mouse haplotypes by the presence of a serine at position 57 of the A beta chain. Identifying islet autoantigens may help elucidate the role of class II antigens in the activation of autoreactive T cells and, thus, in the development of diabetes. We have detected autoantibodies directed against a 58-kDa islet cell antigen in NOD mice but not in other strains, including lupus-prone mice. Apart from insulin-secreting cells, the 58-kDa antigen was only found to be expressed by neuroblastoma cells and was identified as peripherin, an intermediate filament protein previously characterized in well-defined neuronal populations. This autoantigen cross-reacted with I-Anod class II antigens, suggesting that it may contribute to defective self-tolerance of islet beta cells in the NOD mouse.

An improved synthesis of the deoxy-2-fluoroinosine nucleoside is described, that makes use of mild fluorination (polyvinylpyridinium polyhydrogenfluoride) and O-silyl deprotection (triethylamine trihydrofluoride) reactions. The derived 5′-dimethoxytrityl-2-fluoroinosine-3′-phosphoramidite was incorporated into 10-, 15- and 20- mer oligonucleotides containing up to 7 non-natural bases. © 1997 Published by Elsevier Science Ltd.