Biomimetic Strain‐Stiffening Self‐Assembled Hydrogels

Supramolecular structures with strain‐stiffening properties are ubiquitous in nature but remain rare in the lab. Herein, we report on strain‐stiffening supramolecular hydrogels that are entirely produced through the self‐assembly of synthetic molecular gelators. The involved gelators self‐assemble into semi‐flexible fibers, which thereby crosslink into hydrogels. Interestingly, these hydrogels are capable of stiffening in response to applied stress, resembling biological intermediate filaments system. Furthermore, strain‐stiffening hydrogel networks embedded with liposomes are constructed through orthogonal self‐assembly of gelators and phospholipids, mimicking biological tissues in both architecture and mechanical properties. This work furthers the development of biomimetic soft materials with mechanical responsiveness and presents potentially enticing applications in diverse fields, such as tissue engineering, artificial life, and strain sensors.     

Antiproton confinement in a Penning-Ioffe trap for antihydrogen

Antiprotons (p[over]) remain confined in a Penning trap, in sufficient numbers to form antihydrogen (H[over ) atoms via charge exchange, when the radial field of a quadrupole Ioffe trap is added. This first demonstration with p[over] suggests that quadrupole Ioffe traps can be superimposed upon p[over] and e(+) traps to attempt the capture of H[over] atoms as they form, contrary to conclusions of previous analyses.     

The interacting Boson Model applied to the mercury isotopes

The even isotopes of mercury have been systematically studied using the Interacting Boson Model (IBM). In order to treat shape coexistence in the light isotopes, two separate IBM calculations were performed with different configurations, which were subsequently mixed. The four Hamiltonian parameters, which were allowed to vary freely from isotope to isotope, were found to be consistent with the corresponding IBM parameters used for platinum and osmium. Overall, the calculated energy spectra and electromagnetic properties are in reasonable agreement with experiment.     

Selective in vitro glycosylation of recombinant proteins: semi-synthesis of novel homogeneous glycoforms of human erythropoietin

BACKGROUND: A natural glycoprotein usually exists as a spectrum of glycosylated forms, where each protein molecule may be associated with an array of oligosaccharide structures. The overall range of glycoforms can have a variety of different biophysical and biochemical properties, although details of structure-function relationships are poorly understood, because of the microheterogeneity of biological samples. Hence, there is clearly a need for synthetic methods that give access to natural and unnatural homogeneously glycosylated proteins. The synthesis of novel glycoproteins through the selective reaction of glycosyl iodoacetamides with the thiol groups of cysteine residues, placed by site-directed mutagenesis at desired glycosylation sites has been developed. This provides a general method for the synthesis of homogeneously glycosylated proteins that carry saccharide side chains at natural or unnatural glycosylation sites. Here, we have shown that the approach can be applied to the glycoprotein hormone erythropoietin, an important therapeutic glycoprotein with three sites of N-glycosylation that are essential for in vivo biological activity. RESULTS: Wild-type recombinant erythropoietin and three mutants in which glycosylation site asparagine residues had been changed to cysteines (His(10)-WThEPO, His(10)-Asn24Cys, His(10)-Asn38Cys, His(10)-Asn83CyshEPO) were overexpressed and purified in yields of 13 mg l(-1) from Escherichia coli. Chemical glycosylation with glycosyl-beta-N-iodoacetamides could be monitored by electrospray MS. Both in the wild-type and in the mutant proteins, the potential side reaction of the other four cysteine residues (all involved in disulfide bonds) were not observed. Yield of glycosylation was generally about 50% and purification of glycosylated protein from non-glycosylated protein was readily carried out using lectin affinity chromatography. Dynamic light scattering analysis of the purified glycoproteins suggested that the glycoforms produced were monomeric and folded identically to the wild-type protein. CONCLUSIONS: Erythropoietin expressed in E. coli bearing specific Asn-->Cys mutations at natural glycosylation sites can be glycosylated using beta-N-glycosyl iodoacetamides even in the presence of two disulfide bonds. The findings provide the basis for further elaboration of the glycan structures and development of this general methodology for the synthesis of semi-synthetic glycoproteins.     

A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank

Reverse turns are often recognition sites for protein/protein interactions and, therefore, valuable potential targets for determining recognition motifs in development of potential therapeutics. A virtual combinatorial library of cyclic tetrapeptides (CTPs) was generated and the bonds in the low-energy structures were overlapped with canonical reverse-turn Calpha-Cbeta bonds (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005) to determine the utility of CTPs as reverse-turn peptidomimetics. All reverse turns in the Protein Data Bank (PDB) with a crystal structures resolution < or = 3.0 A were classified into the same known canonical reverse-turn Calpha-Cbeta bond clusters (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005). CTP reverse-turn mimics were compiled that mimicked both the relative orientations of three of the four as well as all four Calpha-Cbeta bonds in the reverse turns of the PDB. 54% of reverse turns represented in the PDB had eight or more CTPs structures that mimicked the orientation of all four of the Calpha-Cbeta bonds in the reverse turn.     

Staggered sheaves on partial flag varieties

Staggered t-structures are a class of t-structures on derived categories of equivariant coherent sheaves. In this Note, we show that the derived category of coherent sheaves on a partial flag variety, equivariant for a Borel subgroup, admits a staggered t-structure with the property that all objects in its heart have finite length. As a consequence, we obtain a basis for its equivariant K-theory consisting of simple staggered sheaves. To cite this article: P.N. Achar, D.S. Sage, C. R. Acad. Sci. Paris, Ser. I 347 (2009).     

Spectroscopic characterisation and identification of ecdysteroids using high-performance liquid chromatography combined with on-line UV--diode array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time of flight mass spectrometry

A prototype multiply hyphenated reversed-phase HPLC system has been applied to the analysis of a mixture of pure ecdysteroids and an ecdysteroid-containing plant extract. Characterisation was achieved via a combination of diode array UV, ¹H NMR, FT-IR spectroscopy and time of flight (TOF) mass spectrometry. This combination of spectrometers allowed the collection of UV, ¹H NMR, IR and mass spectra for a mixture of pure standards enabling almost complete structural characterisation to be performed. The technique was then applied to a partially purified plant extract in which 20-hydroxyecdysone and polypodine B were identified despite incomplete chromatographic resolution and the presence of co-chromatographing interferents. The experimental difficulties in the use of such a systems for these analytes are described.     

Long-range reactive dynamics in myoglobin

We report the complete vibrational spectrum of the probe nucleus 57Fe at the oxygen-binding site of the protein myoglobin. The Fe-pyrrole nitrogen stretching modes of the heme group, identified here, probe asymmetric interactions with the protein environment. Collective oscillations of the polypeptide, rather than localized heme vibrations, dominate the low frequency region. We conclude that the heme "doming" mode is significantly delocalized, so that distant sites respond to oxygen binding on vibrational time scales. This has ramifications for understanding long-range interactions in biomolecules, such as those that mediate cooperativity in allosteric proteins.     

Laterally fluorinated phenyl biphenylcarboxylates; versatile components for ferroelectric smectic C mixtures

Twenty-six fluoro-substituted 4-n-alkoxyphenyl 4'-n-alkyi-and 4'-n-alkoxybiphenyl-4-carboxylates are reported. The number and position of the fluoro groups influences the liquid crystal phase sequence and has a dramatic effect on the liquid crystal transition temperatures. Some compounds have low melting points and a very wide smectic C phase, whereas other compounds exhibit a very wide smectic A phase. Compounds containing a 2,3-difluorophenyl group provide useful materials which have a large negative dielectric anisotropy.