Adeno-associated virus (AAV) vectors have become an important tool for delivering therapeutic genes for a wide range of neurological diseases. AAV serotypes possess differential cellular tropism in the central nervous system. Although several AAV serotypes or mutants have been reported to transduce the brain efficiently, conflicting data occur across studies with the use of various rodent strains from different genetic backgrounds.
View Article and Find Full Text PDFAdeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions.
View Article and Find Full Text PDFIt has been demonstrated that human serum albumin (HSA) directly interacts with AAV virions and enhances AAV transduction. Several other proteins have also been identified a potential for enhancing AAV8 liver transduction. In our study, LDL or transferrin could enhance transduction in vitro and in vivo.
View Article and Find Full Text PDFThe syntheses and single-crystal X-ray structures of the mononuclear complexes [Cu(bmet)](ClO4)2·H2O, [Cu(bmet)]Br2·2MeCN, and [Zn(bmet)](ClO4)2·H2O (bmet = N,N'-bis(2,2'-bipyridin-6-ylmethyl)ethane-1,2-diamine) are described. All three complexes feature a central metal ion bound to all six N atoms of the bmet ligand, which displays a meridional-facial-facial-meridional (mffm) configuration. The three complexes show one N-M-N axis to be significantly shorter than the others in agreement with an apparent compressed octahedral geometry.
View Article and Find Full Text PDFDisulfide/thiolate interconversion supported by transition-metal ions is proposed to be implicated in fundamental biological processes, such as the transport of metal ions or the regulation of the production of reactive oxygen species. We report herein a mononuclear dithiolate Co(III) complex, [Co(III)LS(Cl)] (1; LS=sulfur containing ligand), that undergoes a clean, fast, quantitative and reversible Co(II) disulfide/Co(III) thiolate interconversion mediated by a chloride anion. The removal of Cl(-) from the Co(III) complex leads to the formation of a bis(μ-thiolato) μ-disulfido dicobalt(II) complex, [Co2(II,II)LSSL](2+) (2(2+)).
View Article and Find Full Text PDFThe structural and electronic properties as well as the catalytic activity toward sulfoxidation of two new vanadium complexes have been investigated. They both possess in their coordination sphere two alkyl thiolate ligands: a dioxido V(V) complex [VO2L(NS2)](HNEt3) (1) (L(NS2) = 2,2'-(pyridine-2,6-diyl)bis(1,1'-diphenylethanethiol)) and an oxido V(IV) complex [VOL(N2S2)] (2) (L(N2S2) = 2,2'-(2,2'-bipyridine-6,6'-diyl)bis(1,1'-diphenylethanethiol)). The X-ray structure of 1 has revealed that the V(V) metal ion is at the center of a distorted trigonal bipyramid.
View Article and Find Full Text PDFThe structural, spectroscopic, redox properties and also the reactivity toward S-alkylation of a new mononuclear N2S2 dithiolate Co(II) complex [CoL] (1), with H(2)L = 2,2'-(2,2'-bipyridine-6,6'-diyl)bis(1,1-diphenylethanethiol), have been investigated. The X-ray structure of 1 has revealed an unusual distorted square planar geometry for a Co(II) ion within a thiolate environment. The X-band EPR spectrum of displays a rhombic S = 1/2 signal consistent with a low spin configuration for the d(7) Co(II) ion with a large g-anisotropy (g(x) = 2.
View Article and Find Full Text PDFThe synthesis of the new potentially hexadentate ligands N,N'-bis(2,2'-bipyridin-6-ylmethyl)butane-1,4-diamine (bmbu), N,N'-bis(2,2'-bipyridin-6-ylmethyl)pentane-1,5-diamine (bmpt) and N,N'-bis(2,2'-bipyridin-6-ylmethyl)octane-1,8-diamine (bmot) from the condensation of 2,2'-bipyridine-6-carbaldehyde with the appropriate diamine (butane-1,4-diamine, pentane-1,5-diamine and octane-1,8-diamine, respectively) and subsequent reduction, is reported. Bmet, bmpp and bmbu all form mononuclear complexes with first-row transition metal ions (Co(3+), Fe(2+), Ni(2+), Mn(2+)), and X-ray structures of [Mn(bmet)](ClO(4))(2), [Ni(bmet)](ClO(4))(2), [Fe(bmet)](ClO(4))(2), [Mn(bmpp)](ClO(4))(2)·2MeCN and [Co(bmpp)](ClO(4))(3)·H(2)O are reported. As the aliphatic methylene chain increases in length, formation of dinuclear, and in some cases trinuclear, complexes becomes more pronounced, as evidenced by mass spectral analysis of solutions containing Ni(2+) and bmpt, and Ni(2+), Fe(2+) and Mn(2+) with bmot.
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