Arylsulfimide Polymers. IV. Prototype Transamidations–A Comparison of the Reactions of Benzamides,Benzimides, Sulfonamides,Sulfonimides, and Saccharins

Transamidation reactions of nonpolymerizing systems involving benzamides, phthalimides, arylsulfonamides, benzenedisulfonamides and -disulfonim-ides, and saccharins are described. The study includes reactions of both N-substituted and unsubstituted amides and imides with anilines and aniline hydrochlorides. An evaluation of the results of these reactions, aimed at establishing the optimum conditions for transamidations in polymerizing systems, is also presented.     

Synthesis and Properties of Poly(4,8-dialkoxy-1,5-naphthalenevinylene)s

Novel conjugated materials, poly(4,8-dialkoxy-1,5-naphthalenevinylene)s (OC_n-PNV, n = 4, 6, 8, and 12), have been prepared by a method similar to the Gilch procedure. The structure, optical and thermal properties of these polymers with various alkoxy side chain lengths have been evaluated by IR, UV-Vis absorption, fluorescence emission and thermogravimetric analysis. The band gap of OC_n-PNV increases with increasing side chain length. Moreover, wavelengths of the photoluminescence (PL) emission peaks (λ_max) of OC_n-PNV solutions decrease with increasing alkoxy side chain length. This is probably due to the entanglement of long side chains that causes distortion of the conjugated main chains and thereby raises band gap of the polymer. PL λ_max's of these polymers in film state are red-shifted by 14–59 nm than those in solution state. The red-shift is due to the more chain aggregations after spin coating from solution into film state and consequently the lower band gap in the film state. Besides, the polymer with shorter side chains is more thermally stable than that with longer side chains.     

Fine Tuning of Heme Reactivity: Hydrogen-Bonding and Dipole Interactions Affecting Ligand Binding to Hemoproteins

Heme reactivity in hemoproteins is governed by the microenvironment near the ligand binding site. In order to quantify polarity effects on heme ligand binding, the kinetics of O₂ and CO binding have been measured for a series of synthetic heme models equipped with a range of groups of varying dipole moments positioned near the heme coordination site. For hemes with polar aprotic groups, both O₂ on (k′) and off rates (k) are found to be dependent on the dipole moment. For model systems containing protic groups, the O₂ off rate is substantially reduced due to hydrogen bonding with the coordinated O₂. The hydrogen-bonding stabilization is estimated to be 0.7 and 1.6 kcal/mol for an alcohol and a secondary amide, respectively. CO binding displays little correlation with a polarity effect; instead it seems to depend upon the size and position of the polar group.     

Preparation and Characterization of PVC-based Photoresponsive Polymers Containing Azo-chromophores

New strategy was developed for the preparation of the photoresponsive polymers containing azo-chromophores as side-groups from the active chlorine atoms of polyvinyl chloride (PVC). The anilinated polyvinyl chloride precursors, anilinated polyvinyl chloride (PVC-An) and o-chloroanilinated polyvinyl chloride (PVC-oClAn), synthesized chemically by reacting PVC with sodium aniline (o-chloroaniline) salt. Then the two novel PVC-based polymers functionalized with azo-chromophores (PVC-AZ-An and PVC-o-AZ-NP) were synthesized via the azo-coupling reactions of the anilinated polyvinyl chloride precursors (PVC-An and PVC-oClAn) with the diazonium salts of aniline and alpha naphthylamine, respectively. The structures of polymers were confirmed by FTIR and ¹H–NMR. The UV-Vis spectra of the obtained polymer in THF solution showed that the π ?π ? absorption band of PVC-o-AZ-NP shifted to longer wavelength (red-shifted) due to the influence of auxochrome (-Cl) compared to the π ?π ? absorption band of PVC-AZ-An.     

Effects of Bis(aromatic) Pendants on Recognition of Nucleobase Thymine by Zn2+ -1,4,7,10-tetraazacyclododecane (Zn2+ -cyclen)

We have previously shown that the nucleobase thymine binding to Zn²⁺ -cyclen (cyclen=1,4,7,10-tetraazacyclododecane) complex became stronger by appending acridine, naphthalene, or quinoline rings to the cyclen. Amongst these, the pendant bis((1-naphthyl)methyl) or bis((4-quinolyl)methyl) groups yielded the most effective thymine-recognizing Zn²⁺ -cyclen complexes [J. Am. Chem. Soc., 121 (1999) 5426]. The present study was undertaken to find causes of the bis(aromatic) ring effect by X-ray crystal structure analysis and NMR studies. The crystal structure of the Zn²⁺ -bis((1-naphthyl)methyl)-cyclen complex with a deprotonated 1-methylthymine (1-MeT) failed to show the anticipated evidence for the double ~ - ~ stacking interactions between the two naphthalenes and the Zn 2+ -bound 1-MeT m (1-MeT m =N(3')-deprotonated 1-MeT). Crystal data: formula C₃₆ H₄₇ N₇ O₇ Zn, M r =755.19, monoclinic, space group P2₁/ c (No. 14), a =15.438(2) Å, b =14.093(3) Å, c =16.726(2) Å, g =90.53(1) V =3638.7(8) Å 3 Z =4, R =0.035, R _w =0.049. However, the ¹H NMR studies of Zn²⁼ -bis((4-quinolyl)methyl)-cyclen with 1-MeT in varying H₂O/CH₃ CN solution showed increasing upfield shifts of Me(5') and H(6') of the Zn²⁺ -bound 1-MeT in more aqueous media, indicating that the double intercalation with the two quinolines became more significant in more protic environments. We conclude that the double ~ - ~ stacking effect accounts for the enhanced recognition of thymine base by the appended bis((1-naphthyl)methyl) or bis((4-quinolinyl)methyl) groups.     

Prediction of the global energy minimum conformation of polypeptides by the High Directional Monte Carlo procedure

Abstract

A new Monte Carlo sampling scheme, namely High Directional Monte Carlo procedure, is used to obtain the global energy minimum conformations of polypeptides such as enkephalin and melittin. The resultant structures of enkephalin and melittin agree well with previous results of theoretical and experimental studies. Particularly, it is shown that some important parts in the conformation, such as the hinge region that principally determines the tertiary structure of proteins, are correctly described by the new method. The resultant structures are compared with those of other works and their stereoscopic views are shown.     

Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats

The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.     

Chemoproteomic Discovery of AADACL1 as a Regulator of Human Platelet Activation

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Structural Basis for Carbapenemase Activity of the OXA-23 β-Lactamase from Acinetobacter baumannii

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Retrovirus-mediated transduction of a cytosine deaminase gene preserves the stemness of mesenchymal stem cells

Human mesenchymal stem cells (MSCs) have emerged as attractive cellular vehicles to deliver therapeutic genes for ex-vivo therapy of diverse diseases; this is, in part, because they have the capability to migrate into tumor or lesion sites. Previously, we showed that MSCs could be utilized to deliver a bacterial cytosine deaminase (CD) suicide gene to brain tumors. Here we assessed whether transduction with a retroviral vector encoding CD gene altered the stem cell property of MSCs. MSCs were transduced at passage 1 and cultivated up to passage 11. We found that proliferation and differentiation potentials, chromosomal stability and surface antigenicity of MSCs were not altered by retroviral transduction. The results indicate that retroviral vectors can be safely utilized for delivery of suicide genes to MSCs for ex-vivo therapy. We also found that a single retroviral transduction was sufficient for sustainable expression up to passage 10. The persistent expression of the transduced gene indicates that transduced MSCs provide a tractable and manageable approach for potential use in allogeneic transplantation.