Macrobicyclic cage amine ligands for copper radiopharmaceuticals: a single bivalent cage amine containing two Lys3-bombesin targeting peptides

The synthesis of new cage amine macrobicyclic ligands with pendent carboxylate functional groups designed for application in copper radiopharmaceuticals is described. Reaction of [Cu((NH(2))(2)sar)](2+) (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) with either succinic or glutaric anhydride results in selective acylation of the primary amine atoms of [Cu((NH(2))(2)sar)](2+) to give derivatives with either one or two aliphatic carboxylate functional groups separated from the cage amine framework by either a four- or five-atom linker. The Cu(II) serves to protect the secondary amine nitrogen atoms from acylation, and can be removed to give the free ligands. The newly appended carboxylate functional groups can be used as sites of attachment for cancer-targeting peptides such as Lys(3)-bombesin. The synthesis of the first dimeric sarcophagine-peptide conjugate, possessing two Lys(3)-bombesin peptides tethered to a single cage amine, is presented. This species has been radiolabeled with copper-64 at ambient temperature and there is minimal dissociation of Cu(II) from the conjugate even after two days of incubation in human serum.     

Recent developments in capillary electrophoresis-mass spectrometry of proteins and peptides.

Many researchers have invested considerable efforts toward improving capillary electrophoresis (CE)-mass spectrometry (MS) systems so they can be applied better to standard analyses. This review highlights the developments in CE-MS of proteins and peptides over the last five years. It includes the developments in interfaces, sample-enrichment techniques, microfabricated devices, and some applications, largely in capillary zone electrophoresis (CZE), capillary isoelectric focusing (CIEF) and capillary isotachophoresis formats.     

Reflection of light by metal nanoparticles at electrodes

We present model calculations for the reflection spectrum of an ordered two dimensional array of metallic nanoparticles located near an electrochemical interface. We consider three cases, nanoparticles at: (i) a metal electrode, (ii) a transparent semiconductor electrode, and (iii) an electrified liquid/liquid interface. In the case of a metal electrode, the presence of nanoparticles introduces dips in reflection, whose position and depth are affected by the distance and size of the nanoparticles. For both a transparent semiconductor electrode and a liquid/liquid interface, the presence of nanoparticles enhances reflectivity. The spectra are sensitive to the particle spacing and size. The response from all three systems exhibits a strong dependence on the polarisation of light. The dependence on the angle of incidence reveals shallow dips typical of surface plasmon resonance spectra. These findings suggest diagnostic tools for the detection and characterisation of nanoparticle monolayers on functionalised electrodes, and enable electrovariable optical devices based on the controlled assembly of nanoparticles at interfaces.     

Error bounds for least squares approximation by polynomials

Let f ε Cⁿ⁺¹[−1, 1] and let H[f](x) be the nth degree weighted least squares polynomial approximation to f with respect to the orthonormal polynomials q_k associated with a distribution dα on [−1, 1]. It is shown that if q_n+1/q_n max(q_n+1(1)/q_n(1), −q_n+1(−1)/q_n(−1)), then f − H[f] f^{n + 1} · q_n+1/q_{n + 1}^{(n + 1)}, where · denotes the supremum norm. Furthermore, it is shown that in the case of Jacobi polynomials with distribution (1 − t)^α (1 + t)^β dt, α, β > −1, the condition on q_n+1/q_n is satisfied when either max(α,β) −1/2 or −1 < α = β < −1/2.     

The convergence of product integration rules

A recent theorem due to Nevai on the mean convergence of Lagrange interpolation is used to obtain sufficient conditions for the convergence of quadrature rules for product integration.     

Dynamic pH junction technique for on-line preconcentration of peptides in capillary electrophoresis

A method based on the presence of a dynamic pH junction within the capillary to induce band narrowing for enhanced detection sensitivity for some peptides is presented. This technique is predicated on a sharp reduction in an analyte's migration velocity following a reversal of its electrophoretic direction from the acidic sample zone to the basic BGS zone. Larger-than-usual injection volumes of samples in relatively high-conductivity matrices were enabled, without degrading peak shape, resolution and efficiency. The size of the original sample plug was reduced by as much as 38-fold, and improvement in detector response in terms of peak height by as much as 124-fold was obtained. The effects of pH and concentration of the sample matrix, and the length of sample injection on the efficiency of the technique are discussed.     

Bayesian Models Leveraging Bioactivity and Cytotoxicity Information for Drug Discovery

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Highlights? Including efficacy and cytotoxicity data improves performance of computational models ? Antitubercular hits, leads, and chemical probes were identified using Bayesian models ? The most advanced compound provides significant in vitro activity and in vivo safety ? Demonstrated orders-of-magnitude higher hit rates than current HTS practices     

?therische ?le und Riechstoffe

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