Synthesis of new bicyclic lactam peptidomimetics by ring-closing metathesis reactions

An efficient and versatile synthetic method for the preparation of new fused bicyclic lactams 3a and 3b is described. The spirane cyclopentane nucleus was easily installed by diallylation of the pyroglutamate derivative 18 followed by ring-closing metathesis (RCM). A more practical and stereoselective method for the allylation of the α-methoxy carbamate 21, involving the use of InCl₃ as a Lewis acid, was developed. In the crucial coupling reaction of the diastereomeric mixture of cis- and trans-pirrolidine derivatives 5a and 5b with N-Cbz vinyl phenylalanine only the cis isomer was found to react. An RCM reaction on the dipeptides 25a and 25b followed by catalytic hydrogenation, gave the final epimeric bicyclic lactams 3a and 3b. The same synthetic sequence on the model compound 7, lacking the spiro cyclopentane nucleus, is also reported.     

Piperazine quaternary diammonium salts as additives to background electrolytes in capillary zone electrophoresis

The differential behavior of five different quaternary mono- and diammonium salts, among the 18 investigated, in modulating the electroendoosmotic flow (EOF) and analyte separations in capillary zone electrophoresis is evaluated. It is found that quaternary diammonium salts with positive charges separated by more than four carbon atoms, while exhibiting a very strong affinity for chromatographic silica beads, to the point of exhibiting Rf values close to zero, display, on the contrary, a very poor affinity for the silica wall of capillaries. Compounds separated only by a C2 unit (i.e., 1,4-dialkyl-1,4-diazoniabicyclo[2,2,2,]octane, salts 17 and 18) show high Rf values due to strong ion pair association. The unique behavior of quaternary monoammonium salts possessing an iodinated alkyl (butyl or octyl) tail (i.e., 1, 6, and 7) is attributed to their ability to be covalently affixed to the silica wall via alkylation of ionized silanols at alkaline pH values. They thus strongly modulate and typically invert the EOF, even when not present in the background electrolyte. On the contrary, all diammonium salts, devoid of such alkyl tails, are unable to modulate the EOF and to prevent analyte binding to the silica wall, since they are rapidly removed from the wall by the voltage gradient. However, if added in small amount to the background electrolyte, they offer excellent separations of mixtures of very similar organic acids and prevent any interaction with the capillary wall.     

Single-strand conformation polymorphism for p53 mutation by a combination of neutral pH buffer and temperature gradient in capillary electrophoresis

A large number of point mutations in the p53 gene have been detected by capillary zone electrophoresis via single-strand conformation polymorphism (SSCP) analysis. A much improved detection sensitivity was obtained via the following modifications in running conditions: use of low-viscosity 3% hydroxyethylcellulose (HEC), a neutral pH (pH 6.8) buffer, in which the standard Tris moiety was substituted with a 2-(N-morpholino)ethanesulfonic acid (MES)/Tris mixture, use of SYBR Green II for improved fluorescent signal at the lower pH adopted; and, finally, the use of a temperature gradient in the 15-25 degrees C interval, for favoring the conformational transitions in the mutated samples. The typical temperature gradient activated had a slope of 2 degrees C/min and were induced externally. A total of 24 samples from affected patients, both in the homo- and heterozygous state, were analyzed. All the mutations could be detected by this improved protocol, raising the sensitivity from the standard ca. 80% of conventional SSCP to essentially 100% with the present methodology. All the mutations were confirmed by sequence analysis of the affected samples.     

Diffusion coefficients of proteins in carrier ampholyte versus immobiline gels

The apparent diffusion coefficients of proteins in carrier ampholyte isoelectric focusing (CA-IEF) and in immobilized pH gradients (IPGs) are strongly dependent on the amount of buffering ions present in the system. However, whereas in CA-IEF increased levels of ampholytes facilitate diffusion, in IPGs they strongly quench it. It is concluded that a protein in an IPG matrix is isoelectric but not isoionic, in the sense that it forms a salt with the surrounding ions bound to the polyacrylamide matrix. This salt formation is beneficial as it greatly increases protein solubility at the pI. It is suggested that, when performing zymograms in situ, the IPG gel should contain at least twice the standard amount of Immobiline, so as to keep sharp enzyme bands even with prolonged incubation periods.     

Asymmetric base pairing in the complex 5-fluorocytosinium chloride/5-fluorocytosine monohydrate

The structure of the complex 5-Fluorocytosinium chloride/5-Fluorocytosine monohydrate has been studied by X-ray diffraction methods. It crystallizes in the monoclinic system, space group P 2₁ /n, a = 7.1257 (15), b = 8.351 (3), c = 21.520 (4) ?, β = 92.89 (8)°, V = 1279.0 (6) ?³, Z = 4. The structure consists of triple hydrogen-bonded 5-Fluorocytosine pairs, water molecules and chloride anions. Asymmetric reversed Watson-Crick base pairing occurs between one protonated (5FcytH⁺) and one neutral 5-Fluorocytosine (5Fcyt) molecule.     

A semiorthogonal decomposition for Brauer–Severi schemes

A semiorthogonal decomposition for the bounded derived category of coherent sheaves on a Brauer–Severi scheme is given. It relies on bounded derived categories of suitably twisted coherent sheaves on the base (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Lower semicontinuity for quasiconvex integrals of higher order

We consider a functional of the type , where is an open bounded set of and F is a Carathéodory function. By an approximation argument we prove the lower semincontinuity of with respect to the weak topology of under p-growth conditions for the integrand F. Received November 8, 1997     

Measurement of the η production in proton-proton collisions with the COSY time-of-flight spectrometer

The reaction pp → ppη was measured at excess energies of 15 and 41 MeV at an external target of the Jülich Cooler Synchrotron COSY with the time-of-flight spectrometer. About 25000 events were measured for the excess energy of 15 MeV and about 8000 for 41 MeV. Both protons of the process ppη were detected with an acceptance of nearly 100% and the η was reconstructed by the missing-mass technique. For both excess energies the angular distributions are found to be nearly isotropic. In the invariant-mass distributions strong deviations from the pure phase space distributions are seen. Received: 24 May 2002 / Accepted: 20 September 2002 / Published online: 17 January 2003 RID="a" ID="a"e-mail: e.roderburg@fz-juelich.de Communicated by M. Gar?on     

A comparative chemotaxonomic study on Vinca sardoa steam and Vinca difformis pourret

The phytochemical analysis of iridoidic fraction of the aerial parts of Vinca sardoa and Vinca difformis, gave the identification of loganic acid in V. difformis as unique iridoid glucoside, while loganin is also present in V. sardoa. The two taxa highly differ in alkaloids, so the chemotaxonomic classification in two different species is supported.