New renin inhibitors with pseudodipeptidic units in P(1)-P(1') and P(2')-P(3') positions

A series of four new potential renin inhibitors has been synthesized. The structure of the compounds was designed in such a way as to produce agents resistant to enzymatic degradation, metabolically stable, possibly potent and with improved oral absorption. All positions of the 8-13 fragment of the human angiotensinogen were occupied by unnatural units (two unnatural amino acids in positions P(3) and P(2) and two pseudodipeptides in positions P(1)-P(1') and P(2')-P(3')). Both N- and C-terminal functions of the inhibitors were blocked with tert-Boc and ethyl ester groups. Their hydrophobicity evaluated as a log P value, calculated by a computer method, was 6.57 and 6.08 respectively. All peptides were obtained by the carbodiimide method in solution and purified by chromatography on the SiO(2) column. Their resistance to enzymatic degradation was assayed by determination of stability against chymotrypsin activity. The potency was measured in vitro by a spectrofluorimetric method (assay of Leu-Val-Tyr-Ser released from the N-acetyltetradecapeptide substrate by renin in the presence of the inhibitor). All inhibitors were stable to chymotrypsin. Their IC(50) (M/l) values were: 9.6 x 10(-4) (12), 1.6 x 10(-5) (17), 1.0 x 10(-5) (22) and 1.0 x 10(-5) (23) respectively.     

Spirans—XIII : UV—absorption of some spirans

UV absorption spectra of some spirans and their “half-compounds” have been obtained and their comparison has allowed the dominating conformation to be defined for respective spirans.     

Dielectric resonator-based side-access probe for muscle fiber EPR study

We present a novel dielectric resonator (DR)-based resonant structure that accommodates aqueous sample capillaries in orientations that are either parallel (i.e., side-access) or perpendicular to the direction of an external (Zeeman) magnetic field, B(0). The resonant structure consists of two commercially available X-band DRs that are separated by a Rexolite spacer and resonate in the fundamental TE(01delta) mode. The separator between the DRs is used to tune the resonator to the desired frequency and, by appropriately drilled sample holes, to provide access for longitudinal samples, notably capillaries containing oriented, spin-labeled muscle fibers. In contrast to the topologically similar cylindrical TE(011) cavity, the DR-based structure has distinct microwave properties that favor its use for parallel orientation of lossy aqueous samples. For perpendicular orientation of a dilute (6.25 microM) aqueous solution of IASL spin label, the S/N ratio was at least one order of magnitude better for the side-access DR-based structure than for a standard TE(102) cavity. EPR spectra acquired for maleimide spin-labeled myosin filaments also revealed ca. 10 times better S/N ratio than those obtained with a standard TE(102) cavity. For the side-access DR with sample capillaries oriented either parallel or perpendicular to the external magnetic field, the Q- and filling factors are in good agreement with the theoretical estimates derived from the distribution of magnetic (H(1)) and electric (E(1)) components.     

Invariant dependence structures and Archimedean copulas

We consider a family of copulas that are invariant under univariate truncation. Such a family has some distinguishing properties: it is generated by means of a univariate function; it can capture non-exchangeable dependence structures; it can be easily simulated. Moreover, such a class presents strong probabilistic similarities with the class of Archimedean copulas from a theoretical and practical point of view.     

Surface modification of hydroxyapatite for hydrogen generation

Hydrogen provides a safe and clean alternative to carbon-based fuels. Having the proper catalytic support for production of hydrogen is a valuable technology. We report on the surface modification of hydroxyapatite as a novel catalytic support material for hydrogen generation. Aside from being inexpensive and durable, we reveal that Ru ion exchange on the HAP surface provides a highly active support for sodium borohydride hydrolysis, exemplifying a high total turnover number on the order of 24,000 mol H(2)/mol Ru. Moreover, we observe that the RuHAP support exhibits a long catalytic lifetime of approximately 1month upon repeated exposure to NaBH(4) solutions. We identified the ability of complex surface morphology to enhance hydrolysis by the catalytic transition metal covered surface. Particularly, we found that the complex morphology of polycrystalline RuHAP catalytic supports exhibits shorter induction times for hydrogen generation as well as improved reaction rates as compared with single crystal supports possessing the same Ru content. By decreasing induction time and enhancing catalytic activity, we find it feasible to further explore this catalyst support in the construction of a practical hydrogen generation system.     

Effect of light on soluble guanylyl cyclase activity in Pharbitis nil seedlings

Cyclic GMP acts as a chemical switch in plant cells to modulate cellular reactions. However, its metabolism has not been extensively explored and is still poorly understood. Previous experiments suggest that an endogenous cGMP system could participate in the mechanism of phytochrome controlled photoperiodic flower induction in Pharbitis nil. In order to gain further information on the role of cGMP, we have begun to study the enzyme of cGMP synthesis. In this article, the presence of the enzyme with guanylyl cyclase (GC) activity in soluble protein fractions of P. nil is reported. A large portion of the enzymatic activity is present in the cotyledons, where enzyme activity amounted to 0.45 pmol cGMP/min/mg protein. The enzyme exhibited a K(m) 0.5mM for GTP. A plot of 1/v versus 1/[GTP] was linear and V(max) was 0.74 pmol cGMP/min/mg protein. It was shown that the anti-sGC antibody recognise a 40 kDa protein. Moreover, the NO-donor, sodium nitroprusside (SNP) and YC-1, as a NO-independent stimulator, enhanced enzyme activity. The NS 2028 (a potent GC inhibitor) treatments provoked a 3-fold reduction of the enzyme activity in comparison to the untreated fractions. Furthermore, the influence of light on GC activity was analysed. It was noted that cGMP level increased in cool white light, and darkness inhibited enzyme activity. Exposure to blue light acts to stimulate cGMP formation, whereas in red light a rapid decrease in GC activity was observed that returned to the high level when far-red light was applied after the red light treatment. The results presented in this work strongly argue that an enzyme with guanylyl cyclase activity is present in P. nil organs and its activity is controlled by light via the photoreceptors-dependent pathways.     

A BODIPY-functionalized bimetallic probe for sensitive and selective color-fluorometric chemosensing of Hg(2+)

A new BODIPY dye conjugate has demonstrated selective quenching by mercury over other metal ions. Coupling of this probe to Au-Fe(3)O(4) nanoparticles as well as platinum electrodes offered sensitive systems for suspension and surface based sensing, respectively.