Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.     

Selective Propargylation of Carbonyl Compounds and Imines with Barium Reagents

A Barbier‐type regioselective propargylation of aldehydes and ketones with (3‐bromobut‐1‐ynyl)trimethylsilane has been achieved using reactive barium as a low‐valent metal in THF. Especially in the case of ketones, the corresponding homopropargylic alcohols form almost exclusively. In the reaction of α,β‐unsaturated carbonyl compounds, only 1,2‐adducts have been observed. This method is also applicable to propargylation of imines, and the corresponding homopropargylic amines are obtained regiospecifically in good yields with diastereomeric ratios of up to 87:13.     

Isomorphic electron orbitals for vibronic flexibility in a cyclopropenyl radical molecular device

Summary The vibronic character of this molecular device has been studied using isomorphic electron orbitals. The leading role of the softest vibrational mode for the electron transport process is stressed by the quantum mechanical treatment of the rearrangement operator. The theory was used to investigate the possible function of the soliton valve, which has been suggested as a switching tip. The electronic flexibility of the cyclopropenyl radical with respect to molecular vibrations, which is important for the function of the molecular device, is well characterized by the hardness and softness of the electron structure in terms of the orbital energy-occupation number correlation diagram.     

Synthesis of the new chiral tridentate ligand bis(pyrid-2-ylethyl) menthylphosphine and its use in the palladium-catalyzed allylic alkylations

We describe the synthesis of a new asymmetric P,N,N′-tridentate ligand (bis(pyrid-2-ylethyl) menthylphosphine, BPEMP), containing two pyridyl rings and (1S,2R,5S)-menthylphosphino group. The ligand is obtained in five steps from natural abundant l-menthol. The coordination behavior of the ligand toward cationic (allylic)Pd(II) moiety and its first application in palladium-catalyzed asymmetric allylic alkylation are presented. Crystallographic and spectroscopic analyses reveal that [(η³-allylic)Pd(BPEMP)]⁺ complex forms only one isomer in the solid state as well as in solution.     

Improved method for the determination of kynurenic acid in rat plasma by column-switching HPLC with post-column fluorescence detection

Kynurenic acid (KYNA), an endogenous antagonist of ionotropic glutamate and α7 nicotinic receptors, was fluorometrically determined by column-switching high-performance liquid chromatography (HPLC) with fluorescence detection. The HPLC system consists of two octadecyl silica (ODS) columns, both of which are connected with an anion-exchange column (trapping column). Following sample injection onto the HPLC column, KYNA was separated on the first ODS column with a mobile phase of H₂O/acetonitrile (95/5) containing 0.1% acetic acid. The peak fraction of KYNA was trapped on the anion-exchange column by changing the position of a six-port valve and then introduced into the second ODS column. Subsequently, KYNA was detected fluorometrically as a fluorescence complex formed with zinc ion which was pumped constantly. Instrumental limit of detection was approximately 0.16 nM, which corresponded to 8.0 fmol (per 50 μl injection, signal to noise ratio 3), and the limit of quantification was 0.53 nM (signal to noise ratio 10). Intra- and inter-day relative standard deviations were 1.1-3.9% (n = 3) and 3.0-5.3% (n = 3), respectively. The peak of KYNA in rat plasma was clearly detected by the proposed column-switching HPLC system after a facile pretreatment procedure. Intra- and inter-day relative mean errors were −1.6-1.4% (n = 3) and −2.4 to −0.4% (n = 3), respectively, with a satisfactory precision (within 5.0%). A calibration curve for the determination of KYNA showed a good linearity (r² > 0.999) in the range of 25-200 nM. The KYNA concentrations in the plasma of male Sprague-Dawley rats (8-week-old) were 44 ± 5.5 nM (mean ± S.E., n = 5). In ketamine-treated rats, which are animal models of schizophrenia, the plasma KYNA concentrations were significantly increased compared with those in the control rats (p < 0.05).     

Selective formation of AAB- and ABC-type heterotrimeric alpha-helical coiled coils

The alpha-helical coiled coils have a representative amino acid sequence of (abcdefg)(n) heptad repeats. We previously reported that two peptides named IZ-2A and IZ-2W formed an (IZ-2A)(2)/IZ-2W heterotrimer with an Ala-Ala-Trp interaction in the hydrophobic core. In this paper, we describe the selective formation of AAB- and ABC-type heterotrimers. To increase the selectivity of the AAB-type heterotrimeric formation, Lys residues at the f position were mutated to either an Ala or a Gln residue to form IZ-2A(fA) or IZ-2W(fQ). Separately, both IZ-2A(fA) and IZ-2W(fQ) have a random structure at pH 7 and 20 degrees C. However, together IZ-2A(fA) and IZ-2W(fQ) form a 2:1 complex with a thermal transition midpoint (Tm) of 48 degrees C. This procedure was applied to prepare the ABC-type heterotrimer, in which two sets of Ala-Ala-Trp interactions were designed in the hydrophobic core. Interhelical interaction between the e and g positions and the alpha-helical propensity of the amino acid at the f position were also considered in the design. The resultant three peptides selectively formed the ABC-type heterotrimer with a Tm of 51 degrees C. Other peptide combinations had random coil properties.     

An anthracene-based Cd fluorescent chemosensor with a 4,7-bis(2-hydroxyethyl)-9-hydroxy-1,4,7-triazanonyl group as a highly selective chelator to Cd over Zn

We have developed a Cd²⁺ fluorescent chemosensor with high selectivity as well as sensitivity by tethering a 4,7-bis(2-hydroxyethyl)-9-hydroxy-1,4,7-triazanonyl chelator to anthracene. This sensor features the ability to discriminate Cd²⁺ from Zn²⁺ to a high degree (K_dZn/K_dCd = 560) in a pH 7.2 buffer.     

Dissipative structure for symmetric hyperbolic systems with memory

We study symmetric hyperbolic systems with memory-type dissipation and investigate their dissipative structures. We treat two cases: memory-type diffusion and memory-type relaxation, and observe that the dissipative structures of these two cases are essentially different. Namely, we show that the dissipative structure of the system with memory-type diffusion is of the standard type, while that of the system with memory-type relaxation is of the regularity-loss type.