29 research outputs found
Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases
Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins
Variable Nitric Oxide Reactivity of Tropocoronand Cobalt(III) Nitrite Complexes as a Function of the Polymethylene Linker Chain Length
The size-dependent reactivity of cobalt tropocoronands
[TC-<i>n</i>,<i>n</i>]<sup>2–</sup> is
manifest in
the NO chemistry of the cobalt(III) nitrite complexes [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-<i>n</i>,<i>n</i>)]
(<i>n</i> = 4–6), the synthesis and characterization
of which are reported for the first time. Complete conversion of [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-4,4)] to the cobalt mononitrosyl [Co(NO)(TC-4,4)]
occurs upon exposure to NO(g). In contrast, addition of NO(g) to [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-5,5)] generates both cobalt mono- and
dinitrosyl adducts, and addition of nitric oxide to [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-6,6)] converts this complex to the dicobalt
tetranitrosyl species [Co<sub>2</sub>(NO)<sub>4</sub>(TC-6,6)]. In
the latter complex, two tetrahedral cobalt dinitrosyl units are bound
to the aminotroponeiminate poles of the [TC-6,6]<sup>2–</sup> ligand. These results significantly broaden the chemistry of cobalt
tropocoronands with nitric oxide and the nitrite anion
Influence of Tetraazamacrocyclic Ligands on the Nitric Oxide Reactivity of their Cobalt(II) Complexes
The reactions of cobalt(II) complexes of tetraazamacrocyclic
tropocoronand
(TC) ligands with nitric oxide (NO) were investigated. When [Co(TC-5,5)]
was allowed to react with NO(g), the {CoNO}<sup>8</sup> mononitrosyl
[Co(NO)(TC-5,5)] was isolated and structurally characterized. In contrast,
a {Co(NO)<sub>2</sub>}<sup>10</sup> species formed when [Co(TC-6,6)]
was exposed to NO(g), and the nitrito [Co(NO<sub>2</sub>)(TC-6,6)]
complex was structurally and spectroscopically characterized from
the reaction mixture. The {Co(NO)<sub>2</sub>}<sup>10</sup> species
was assigned
as the bis(cobalt dinitrosyl) complex [Co<sub>2</sub>(NO)<sub>4</sub>(TC-6,6)] by spectroscopic comparison with independently synthesized
and characterized material. These results provide the first evidence
for the influence of tropocoronand ring size on the nitric oxide reactivity
of the cobalt(II) complexes
Variable Nitric Oxide Reactivity of Tropocoronand Cobalt(III) Nitrite Complexes as a Function of the Polymethylene Linker Chain Length
The size-dependent reactivity of cobalt tropocoronands
[TC-<i>n</i>,<i>n</i>]<sup>2–</sup> is
manifest in
the NO chemistry of the cobalt(III) nitrite complexes [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-<i>n</i>,<i>n</i>)]
(<i>n</i> = 4–6), the synthesis and characterization
of which are reported for the first time. Complete conversion of [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-4,4)] to the cobalt mononitrosyl [Co(NO)(TC-4,4)]
occurs upon exposure to NO(g). In contrast, addition of NO(g) to [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-5,5)] generates both cobalt mono- and
dinitrosyl adducts, and addition of nitric oxide to [Co(η<sup>2</sup>-NO<sub>2</sub>)(TC-6,6)] converts this complex to the dicobalt
tetranitrosyl species [Co<sub>2</sub>(NO)<sub>4</sub>(TC-6,6)]. In
the latter complex, two tetrahedral cobalt dinitrosyl units are bound
to the aminotroponeiminate poles of the [TC-6,6]<sup>2–</sup> ligand. These results significantly broaden the chemistry of cobalt
tropocoronands with nitric oxide and the nitrite anion
Influence of Tetraazamacrocyclic Ligands on the Nitric Oxide Reactivity of their Cobalt(II) Complexes
The reactions of cobalt(II) complexes of tetraazamacrocyclic
tropocoronand
(TC) ligands with nitric oxide (NO) were investigated. When [Co(TC-5,5)]
was allowed to react with NO(g), the {CoNO}<sup>8</sup> mononitrosyl
[Co(NO)(TC-5,5)] was isolated and structurally characterized. In contrast,
a {Co(NO)<sub>2</sub>}<sup>10</sup> species formed when [Co(TC-6,6)]
was exposed to NO(g), and the nitrito [Co(NO<sub>2</sub>)(TC-6,6)]
complex was structurally and spectroscopically characterized from
the reaction mixture. The {Co(NO)<sub>2</sub>}<sup>10</sup> species
was assigned
as the bis(cobalt dinitrosyl) complex [Co<sub>2</sub>(NO)<sub>4</sub>(TC-6,6)] by spectroscopic comparison with independently synthesized
and characterized material. These results provide the first evidence
for the influence of tropocoronand ring size on the nitric oxide reactivity
of the cobalt(II) complexes
Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn<sup>2+</sup> with <i>S</i>-Nitrosothiols and Implications for Nitric Oxide Synthase
Zinc thiolate complexes containing N<sub>2</sub>S tridentate
ligands
were prepared to investigate their reactivity toward reactive nitrogen
species, chemistry proposed to occur at the zinc tetracysteine thiolate
site of nitric oxide synthase (NOS). The complexes are unreactive
toward nitric oxide (NO) in the absence of dioxygen, strongly indicating
that NO cannot be the species directly responsible for <i>S</i>-nitrosothiol formation and loss of Zn<sup>2+</sup> at the NOS dimer
interface in vivo. <i>S</i>-Nitrosothiol formation does
occur upon exposure of zinc thiolate solutions to NO in the presence
of air, however, or to NO<sub>2</sub> or NOBF<sub>4</sub>, indicating
that these reactive nitrogen/oxygen species are capable of liberating
zinc from the enzyme, possibly through generation of the <i>S</i>-nitrosothiol. Interaction between simple Zn<sup>2+</sup> salts and
preformed <i>S</i>-nitrosothiols leads to decomposition
of the −SNO moiety, resulting in release of gaseous NO and
N<sub>2</sub>O. The potential biological relevance of this chemistry
is discussed
Synthesis, Photophysics, Electrochemistry, and Electrogenerated Chemiluminescence of a Homologous Set of BODIPY-Appended Bipyridine Derivatives
Two new 2,2′-bipyridine (bpy)-based ligands with ancillary BODIPY chromophores attached at the 4- and 4′-positions were prepared and characterized, which vary in the substitution pattern about the BODIPY periphery by either excluding (BB1) or including (BB2) a β-alkyl substituent. Both absorb strongly throughout the visible region and are strongly emissive. The basic photophysics and electrochemical properties of BB1 and BB2 are comparable to those of the BODIPY monomers on which they are based. The solid-state structures and electronic structure calculations both indicate that there is negligible electronic communication between the BODIPY moieties and the intervening bpy spacers. Electrogenerated chemiluminescence spectra of the two bpy-BODIPY derivatives are similar to their recorded fluorescence profiles and are strongly influenced by substituents on the BODIPY chromophores. These 2,2′-bipyridine derivatives represent a new set of ligands that should find utility in applications, including light-harvesting, photocatalysis, and molecular electronics.National Institutes of Health (U.S.) (Postdoctoral Fellowship F32 GM080060-02)National Science Foundation (U.S.) (CHE-0907905
Benefits of Using Traffic Volumes Described on Examples in the Open Transport Net Project Pilot Regions
The paper describes the goals of the Open Transport Net project in the pilot regions for regional development and the motivation to use traffic volumes in order to reach the project objectives. In the introduction, a short overview of the Open Transport Net project is provided. It is followed by descriptions of the identified problems in the pilot regions and incentives to use traffic volumes for achieving good quality results. The basics of traffic volumes as well as their visualisation are further described and demonstrated including several examples
1,2-Hydroxypyridonate/Terephthalamide Complexes of Gadolinium(III): Synthesis, Stability, Relaxivity, and Water Exchange Properties
Four new Gd(III) complexes based on the 1,2-hydroxypyridinone chelator have been synthesized and evaluated as potential MRI contrast agents. Previously reported work examining Gd-TREN-1,2-HOPO (3) suggests that the 1,2-HOPO unit binds strongly and selectively to Gd(III), encouraging further study of the stability and relaxivity properties of this class of compounds. Among the new complexes presented in this paper are the homopodal Gd-Ser-TREN-1,2-HOPO (Gd-5) and three heteropodal bis-1,2-HOPO-TAM complexes (Gd-6, Gd-7, and Gd-8). Conditional stability constants were determined and all pGd values are in the range of 18.5 − 19.7, comparable to other analogous HOPO complexes and currently used commercial contrast agents. Relaxivities for all complexes are about twice those of commercial agents, ranging from 7.8 − 10.5 mM(−1)s(−1) (20 MHz; 25 °C), and suggest two inner-sphere water molecules in fast exchange. Luminescent measurements were used to verify the number of coordinated waters for Gd-5, and VT (17)O NMR experiments were employed for the highly soluble Gd-TREN-bis-1,2-HOPO-TAM-N3 (Gd-8) complex to measure a fast water exchange rate, (298)k(ex) = 1/τ(M), of 5.1(±0.4) × 10(8) s(−1) ((298)τ(M) ∼ 2 ns)
Reactions of Organozinc Thiolates with Nitrosonium Ion: <i>C</i>‑Nitroso Formation by Possible Transnitrosation
The organometallic complexes [ZnPAThEt] and [ZnPAThMes],
where PATh is 2-methyl-1-[methyl-(2-pyridin-2-yl-ethyl)amino]propane-2-thiolate,
were prepared and their reactions with NOBF<sub>4</sub> investigated.
Formation of <i>C</i>-nitrosoethane and <i>C</i>-nitrosomesitylene, respectively, was established, and structural
characterization of the latter by X-ray crystallography conclusively
proved the dimeric nature of [MesNO]<sub>2</sub> in the solid state.
A transnitrosation pathway for <i>C</i>-nitroso formation
is proposed based on theoretical calculations