Structural and functional peculiarities of plasminogen activator inhibitor PAI-1

PAI-1, an important component of the hemostasis system, is a specific inhibitor of both urokinase type and tissue type plasminogen activators. PAI-1 belongs to the serpin family. The interaction between somatomedin-like domain of vitronectin and PAI-1 leads to stabilization of the latter. PAI-1 latency transition is related to the conformational changes in the reactive central loop. The inhibitory mechanism of PAI-1 is in accordance with the classic scheme of serpin action. PAI-1 blocks the adhesion mediated by UPA and integrins, so this inhibitor plays an important role in adhesion process and angiogenesis. An altered PAI-1level is associated with the development of cardiovascular diseases, kidney fibrosis, diabetis, cancerogenesis.ПАИ-1,важный компонент системы гемостаза, является специфическим ингибитором активаторов плазминогена тканевого (ТПA) и урокиназного (УПА) типов. ПАИ-1 относится к семейству серпинов. Взаимодействие с соматомединоподобным доменом витронектина стабилизирует ак- тивную форму ингибитора. Переход ПАИ-1 в латентное состояние сопряжен с конформационными изменениями в области петли реактивного центра. Механизм ингибиторного действия ПАИ-1 соответствует классической схеме ингибирования серпинами. ПАИ-1 блокирует адгезию, опосредованную рецептором УПА и интегринами, выполняя при этом важную роль в адгезивных процессах и ангиогенезе. Изменения уровня ПАИ-1 рассматривают как важный прогностический признак при заболеваниях сердечно-сосудистой системы (инфаркт миокарда, инсульт), фиброзе почек, диабете, канцерогенезе.ПАІ-1, важливий компонент системи гемостазу, є специфічним інгібітором активаторів плазміногену тканинного (ТПА) та урокіназного типів. ПАІ-1 належить до серпінової родини. Взаємодія з соматоподібним доменом вітронектину стабілізує активну форму інгібітора. Перехід ПАІ-1 до латентного стану пов’язаний з конформаційними змінами у ділянці петлі реактивного центра. Механізм інгібіторної дії ПАІ-1 відповідає класичній схемі серпінового інгібування. ПАІ-1 блокує адгезію опосередковану рецептором УПА та інтегринами, виконуючи при цьому важливу роль в адгезивних процессах та ангіогенезі. Зміни рівня ПАІ-1 розглядають як істотну прогностичну ознаку при захворюваннях серцево-судинної системи, фіброзі нирок, діабеті, канцерогенезі

L'enseignement et l'édition du droit canonique en France dans la seconde moitié du XIXe siècle : lieux d'expression du "mouvement vers Rome"

International audienceCette contribution revient sur la progressive évolution du catholicisme intransigeant dans les revues et l'enseignement du droit canonique français, entre les pontificats de Pie IX et de Pie X

Chromophores in molecular nanorings : when is a ring a ring?

The topology of a conjugated molecule plays a significant role in controlling both the electronic properties and the conformational manifold that the molecule may explore. Fully π-conjugated molecular nanorings are of particular interest, as their lowest electronic transition may be strongly suppressed as a result of symmetry constraints. In contrast, the simple Kasha model predicts an enhancement in the radiative rate for corresponding linear oligomers. Here we investigate such effects in linear and cyclic conjugated molecules containing between 6 and 42 butadiyne-linked porphyrin units (corresponding to 600 C–C bonds) as pure monodisperse oligomers. We demonstrate that as the diameter of the nanorings increases beyond ∼10 nm, its electronic properties tend toward those of a similarly sized linear molecule as a result of excitation localization on a subsegment of the ring. However, significant differences persist in the nature of the emitting dipole polarization even beyond this limit, arising from variations in molecular curvature and conformation

Height dependent molecular trapping in stacked cyclic porphyrin nanorings

Stacked layers of cyclic porphyrin nanorings constitute nanoscale receptacles with variable height and diameter which preferentially adsorb sublimed molecules. Using scanning tunnelling microscopy we determine the filling capacity of these nanoring traps, and the dependence of adsorbate capture on stack height and diameter

Ordering, Flexibility and Frustration in Arrays of Porphyrin Nanorings

The regular packing of atoms, molecules and nanoparticles provides the basis for the understanding of structural order within condensed phases of matter. Typically the constituent particles are considered to be rigid with a fixed shape. Here we show, through a combined experimental and numerical study of the adsorption of cyclic porphyrin polymers, nanorings, on a graphite surface, that flexible molecules can exhibit a rich and complex packing behaviour. Depending on the number of porphyrin sub-units within the nanoring we observe either a highly ordered hexagonal phase or frustrated packing driven by directional interactions which for some arrangements is combined with the internal deformation of the cyclic polymer. Frustration and deformation occur in arrays of polymers with ten sub-units since close packing and co-alignment of neighbouring groups cannot be simultaneously realised for nanorings with this internal symmetry. *[email protected]

Molecular quantum rings formed from a π-conjugated macrocycle

The electronic structure of a molecular quantum ring (stacks of 40-unit cyclic porphyrin polymers) is characterised via scanning tunnelling microscopy (STM) and scanning tunnelling spectroscopy (STS). Our measurements access the energetic and spatial distribution of the electronic states and, utilising a combination of density functional theory and tight binding calculations, we interpret the experimentally obtained electronic structure in terms of coherent quantum states confined around the circumference of the π-conjugated macrocycle. These findings demonstrate that large (53 nm circumference) cyclic porphyrin polymers have the potential to act as molecular quantum rings

Mechanical stiffening of porphyrin nanorings through supramolecular columnar stacking

Solvent-induced aggregates of nanoring cyclic polymers may be transferred by electrospray deposition to a surface where they adsorb as threedimensional columnar stacks. The observed stack height varies from single rings to four stacked rings with a layer spacing of 0.32 ± 0.04 nm as measured using scanning tunneling microscopy. The flexibility of the nanorings results in distortions from a circular shape, and we show, through a comparison withMonte Carlo simulations, that the bending stiffness increases linearly with the stack height. Our results show that noncovalent interactions may be used to control the shape and mechanical properties of artificial macromolecularaggregates offering a new route to solvent-induced control of two-dimensional supramolecular organization

Vernier-templated synthesis, crystal structure, and supramolecular chemistry of a 12-Porphyrin nanoring

Vernier templating exploits a mismatch between the number of binding sites in a template and a reactant to direct the formation of a product that is large enough to bind several template units. Here, we present a detailed study of the Vernier-templated synthesis of a 12-porphyrin nanoring. NMR and small-angle X-ray scattering (SAXS) analyses show that Vernier complexes are formed as intermediates in the cyclo-oligomerization reaction. UV/Vis/NIR titrations show that the three-component assembly of the 12-porphyrin nanoring figure-of-eight template complex displays high allosteric cooperativity and chelate cooperativity. This nanoring–template 1:2 complex is among the largest synthetic molecules to have been characterized by single-crystal analysis. It crystallizes as a racemate, with an angle of 27° between the planes of the two template units. The crystal structure reveals many unexpected intramolecular C[BOND]H⋅⋅⋅N contacts involving the tert-butyl side chains. Scanning tunneling microscopy (STM) experiments show that molecules of the 12-porphyrin template complex can remain intact on the gold surface, although the majority of the material unfolds into the free nanoring during electrospray deposition

Retaining individualities : the photodynamics of self-ordering porphyrin assemblies

YesThe retention of photochemical properties of individual chromophores is a key feature of biological light harvesting complexes. This is achieved despite extensive aggregation of the chromophores, which in synthetic chromophore assemblies often yields a change in spectral characteristics. As an alternative approach towards mimicking biological light harvesting complexes, we report the synthesis of porphyrin assemblies which retained the photochemical properties of the individual chromophore units despite their substantial aggregation. These new materials highlight a new bottom-up approach towards the design and understanding of more complex biomimetic and naturally occurring biological systems.Seventh Framework Programme (European Commission) (FP7), Engineering and Physical Sciences Research Council (EPSRC), Royal Society (Great Britain