Optical activity produced by layer chirality in bent-core liquid crystals

Large optical activity has recently been observed in chiral smectic liquid crystalline phases formed from achiral bent-core molecules. The origin of the optical activity remains unclear and has been attributed to both a helical superstructure and the layer chirality produced by simultaneous tilt and polar ordering of bent-core mesogens in the B2 phase. Here, we directly demonstrate that layer chirality produces optical activity in the well ordered SmC(A)P(A) subphase.     

Determination of global structure from distance and orientation constraints in biological solids using solid-state NMR spectroscopy

We report the results from a new solid-state NMR experiment, DANTE-REDOR, which can determine global secondary structure in uniformly (13C,15N)-enriched systems by simultaneously measuring distance and orientation constraints. Following a heteronuclear spin-pair selection using a DANTE pulse train, the magnitude and orientation of the internuclear dipole vector, within the chemical shift anisotropy (CSA) frame of the observed nucleus, are determined by tracking the dephasing of individual spinning sidebands under magic angle spinning. The efficacy of the experiment is demonstrated by measuring the imidazole side-chain orientation in U-[13C6,15N3]-L-histidine x HCl x H2O.     

A third mode of DNA binding: Phosphate clamps by a polynuclear platinum complex

We describe a 1.2 A X-ray structure of a double-stranded B-DNA dodecamer (the Dickerson Dodecamer, DDD, [d(CGCGAATTCGCG)]2) associated with a cytotoxic platinum(II) complex, [{trans-Pt(NH3)2(NH2(CH2)6(NH3+)}2-mu-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}] (TriplatinNC). TriplatinNC is a multifunctional DNA ligand, with three cationic Pt(II) centers, and directional hydrogen bonding functionalities, linked by flexible hydrophobic segments, but without the potential for covalent interaction. TriplatinNC does not intercalate nor does it bind in either groove. Instead, it binds to phosphate oxygen atoms and thus associates with the backbone. The three square-planar tetra-am(m)ine Pt(II) coordination units form bidentate N...O...N complexes with OP atoms, in a motif we call the Phosphate Clamp. The geometry is conserved among the 8 observed phosphate clamps in this structure. The interaction appears to prefer O2P over O1P atoms (frequency of interaction is O2P > O1P, base and sugar oxygens > N). The high repetition and geometric regularity of the motif suggests that this type of Pt(II) center can be developed as a modular nucleic acid binding device with general utility. TriplatinNC extends along the phosphate backbone, in a mode of binding we call "Backbone Tracking" and spans the minor groove in a mode of binding we call "Groove Spanning". Electrostatic forces appear to induce modest DNA bending into the major groove. This bending may be related to the direct coordination of a sodium cation by a DNA base, with unprecedented inner-shell (direct) coordination of penta-hydrated sodium at the O6 atom of a guanine.     

Dynamic stark effect in strongly coupled microcavity exciton polaritons

We present experimental observations of a nonresonant dynamic Stark shift in strongly coupled microcavity quantum well exciton polaritons-a system which provides a rich variety of solid-state collective phenomena. The Stark effect is demonstrated in a GaAs/AlGaAs system at 10?K by femtosecond pump-probe measurements, with the blueshift approaching the meV scale for a pump fluence of 2 mJ?cm^{-2} and 50?meV red detuning, in good agreement with theory. The energy level structure of the strongly coupled polariton Rabi?doublet remains unaffected by the blueshift. The demonstrated effect should allow generation of ultrafast density-independent potentials and imprinting well-defined phase profiles on polariton condensates, providing a powerful tool for manipulation of these condensates, similar to dipole potentials in cold-atom systems.     

Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates

The endocannabinoids 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide) are principally degraded by monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. The recent discovery of O-aryl carbamates such as JZL184 as selective MAGL inhibitors has enabled functional investigation of 2-AG signaling pathways in vivo. Nonetheless, JZL184 and other reported MAGL inhibitors still display low-level cross-reactivity with FAAH and peripheral carboxylesterases, which can complicate their use in certain biological studies. Here, we report a distinct class of O-hexafluoroisopropyl (HFIP) carbamates that inhibits MAGL in vitro and in vivo with excellent potency and greatly improved selectivity, including showing no detectable cross-reactivity with FAAH. These findings designate HFIP carbamates as a versatile chemotype for inhibiting MAGL and should encourage the pursuit of other serine hydrolase inhibitors that bear reactive groups resembling the structures of natural substrates.     

Structure Selectivity of Alkaline Periodate Oxidation on Lignocellulose for Facile Isolation of Cellulose Nanocrystals

Reported here for the first time is the alkaline periodate oxidation of lignocelluloses for the selective isolation of cellulose nanocrystals (CNCs). With the high concentrations as a potassium salt at pH 10, periodate ions predominantly exist as dimeric orthoperiodate ions (H₂I₂O₁₀^4?). With reduced oxidizing activity in alkaline solutions, dimeric orthoperiodate ions preferentially oxidized non‐ordered cellulose regions. The alkaline surroundings promoted the degradation of these oxidized cellulose chains by β‐alkoxy fragmentation and generated CNCs. The obtained CNCs were uniform in size and generally contained carboxy groups. Furthermore, the reaction solution could be reused after regeneration of the periodate with ozone gas. This method allows direct production of CNCs from diverse sources, in particular lignocellulosic raw materials including sawdust (European beech and Scots pine), flax, and kenaf, in addition to microcrystalline cellulose and pulp.     

The Molecular Basis of the Interaction of Cyclophilin A with α-Synuclein

Peptidylprolyl isomerases (PPIases) catalyze cis/trans isomerization of prolines. The PPIase CypA colocalizes with the Parkinson's disease (PD)-associated protein α-synuclein in cells and interacts with α-synuclein oligomers. Herein, we describe atomic insights into the molecular details of the α-synuclein/CypA interaction. NMR spectroscopy shows that CypA catalyzes isomerization of proline 128 in the C-terminal domain of α-synuclein. Strikingly, we reveal a second CypA-binding site formed by the hydrophobic sequence ⁴⁷GVVHGVATVA⁵⁶, termed PreNAC. The 1.38 Å crystal structure of the CypA/PreNAC complex displays a contact between alanine 53 of α-synuclein and glutamine 111 in the catalytic pocket of CypA. Mutation of alanine 53 to glutamate, as found in patients with early-onset PD, weakens the interaction of α-synuclein with CypA. Our study provides high-resolution insights into the structure of the PD-associated protein α-synuclein in complex with the most abundant cellular cyclophilin.     

Filamentous phage studied by magic-angle spinning NMR: resonance assignment and secondary structure of the coat protein in Pf1

Assignments are presented for resonances in the magic-angle spinning solid-state NMR spectra of the major coat protein subunit of the filamentous bacteriophage Pf1. NMR spectra were collected on uniformly 13C and 15N isotopically enriched, polyethylene glycol precipitated samples of fully infectious and hydrated phage. Site-specific assignments were achieved for 231 of the 251 labeled atoms (92%) of the 46-residue-long coat protein, including 136 of the 138 backbone atoms, by means of two- and three-dimensional 15N and 13C correlation experiments. A single chemical shift was observed for the vast majority of atoms, suggesting a single conformation for the 7300 subunits in the 36 MDa virion in its high-temperature form. On the other hand, multiple chemical shifts were observed for the Calpha, Cbeta, and Cgamma atoms of T5 in the helix terminus and the Calpha and Cbeta atoms of M42 in the DNA interaction domain. The chemical shifts of the backbone atoms indicate that the coat protein conformation involves a 40-residue continuous alpha-helix extending from residue 6 to the C-terminus.     

Trispectrum for the response of a non-linear oscillator

Simulation is used to obtain information about non-Gaussian aspects of the absolute response acceleration of a bi-linear hysteretic oscillator with an excitation which is Gaussian white noise. Attention is focused on the frequency content of the fourth cumulant of the response. This frequency content is studied by consideration of the trispectrum and also by the simplified technique of looking at the coefficient of excess for the response of a narrowband linear system mounted on the non-linear oscillator. Attempts are also made to model the non-Gaussian response of the non-linear oscillator by a filtered delta correlated (FDC) process, but it is shown that no process of this type can exhibit some of the significant characteristics of the non-linear response. In particular, the trispectrum of the non-linear response appears to be more narrowband than the power spectral density, and also it sometimes does not have the same sign at every point in the three-dimensional frequency space, and this behavior is distinctly different from that of any FDC process. Modifications of the FDC model are suggested in order to obtain improved approximations of the non-linear response.