Partial Colocalization of Oxidized,N-formylkynurenine-containing Proteins in Mitochondria and Golgi of Keratinocytes†

Proteins are the dominant cellular target for oxidative reactions because they comprise the majority of macromolecules. Posttranslational oxidative protein modifications include fragmentation, aggregation and alteration of specific amino acid residues. The amino acids and amino acid residues most susceptible to oxidative modification are those containing sulfur and those with aromatic rings. Tryptophan reacts with radicals, ozone and singlet oxygen to form the end product N-formylkynurenine (NFK). We recently described a novel anti-NFK antiserum and validated its use in immunological assays for the specific detection of NFK in isolated proteins and protein mixtures. Here we photo-oxidize rose bengal-containing HaCaT keratinocyte cells and examine the results using fluorescent confocal microscopy and staining with anti-NFK antiserum and markers for both Golgi and mitochondria. We show that photosensitization mediates the accumulation of NFK and that NFK can be detected in photosensitized cells with only slightly decreased viability. Additionally, we detect NFK-modified proteins in both Golgi and mitochondria of photosensitized cells. These experiments demonstrate that we have developed a tool for the specific detection of oxidized tryptophan residues in cells and suggest that this tool could be useful in tracking the fate of these oxidized proteins.     

Oxidation of Active Methylene Compounds by Pyridinium Chlorochromate

1-Aryl-1,2-diketones 6 have been obtained by pyridinium chlorochromate oxidation of benzylketones 5. In the same way 2-buten-1, 4-olide 2 and 3H-benzofuran-2-one 4 have been obtained.     

Nanostructures for magnetically triggered release of drugs and biomolecules

Specific targeting and controlled release are crucial factors in the administration of drugs and therapeutic biomolecules. It has been shown that drug delivery systems can significantly benefit of the introduction of superparamagnetic nanoparticles in terms of both targeting and controlled release. Magnetic gradients can be used to target therapeutics to specific regions, while alternating magnetic fields produce frequency-dependent effects at the nanoparticle level. This review reports on the latest developments of multifunctional systems based on magnetic nanoparticles where the release of drugs and/or biomolecules is triggered by the application of an external magnetic field. The potentials of these systems are presented through examples in the fields of surface functionalized magnetic nanoparticles, magnetic polymer nanocomposites and magnetoliposomes. Recent results suggest the importance of integrating multiple functions within a single nanostructured device in order to successfully transport, localize and release drugs and biomolecules.     

A chiral electrophilic selenium reagent to promote the kinetic resolution of racemic allylic alcohols

[reaction: see text] The first example of a kinetic resolution process promoted by electrophilic selenium reagents is reported. Racemic allylic alcohols react with half equivalents of a selenenylating agent in methanol leading to the regiospecific formation of the corresponding addition products with a very high level of facial selectivity (from 95:5 to 98:2 dr). The unreacted alcohols can be recovered in an optically enriched form (from 90 to 94% ee).     

Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors

A new protocol is described for the stereocontrolled synthesis of pseudo-C(2)-symmetric core units of interest as candidates for HIV protease inhibition. Addition of unbranched and branched organolithium reagents to cyanohydrins from l-phenylalaninal and l-isoleucinal, followed by in situ reduction of the intermediate imines and CHT deprotection under MW irradiation, led to 1,3-diamino alcohols 6a and 8a as the major products in satisfactory to good yields. The first preparation of a previously unreported pseudo-C(2)-symmetric triamino derivative was accomplished expeditiously via high-yielding nitro-Mannich addition of the silylnitronate, from 2-phenyl-1-nitroethane, to the PMP imine derived from l-phenylalaninal. Reduction of the nitro group in the moderately unstable nitro diamine adduct, followed by chromatographic separation of the required diastereoisomer and CHT debenzylation under MW irradiation, led to the 2-PMP-protected triamine 19 isolated as a bis(sulfonamide).     

Weakly horospherically convex hypersurfaces in hyperbolic space

In Bonini et al. (Adv Math 280:506–548, 2015), the authors develop a global correspondence between immersed weakly horospherically convex hypersurfaces \(\phi :M^n \rightarrow \mathbb {H}^{n+1}\) and a class of conformal metrics on domains of the round sphere \(\mathbb {S}^n\). Some of the key aspects of the correspondence and its consequences have dimensional restrictions \(n\ge 3\) due to the reliance on an analytic proposition from Chang et al. (Int Math Res Not 2004(4):185–209, 2004) concerning the asymptotic behavior of conformal factors of conformal metrics on domains of \(\mathbb {S}^n\). In this paper, we prove a new lemma about the asymptotic behavior of a functional combining the gradient of the conformal factor and itself, which allows us to extend the global correspondence and embeddedness theorems of Bonini et al. (2015) to all dimensions \(n\ge 2\) in a unified way. In the case of a single point boundary \(\partial _{\infty }\phi (M)=\{x\} \subset \mathbb {S}^n\), we improve these results in one direction. As an immediate consequence of this improvement and the work on elliptic problems in Bonini et al. (2015), we have a new, stronger Bernstein type theorem. Moreover, we are able to extend the Liouville and Delaunay type theorems from Bonini et al. (2015) to the case of surfaces in \(\mathbb {H}^{3}\).     

Phonon anharmonicities in graphite and graphene

We determine from first principles the finite-temperature properties-linewidths, line shifts, and lifetimes-of the key vibrational modes that dominate inelastic losses in graphitic materials. In graphite, the phonon linewidth of the Raman-active E(2g) mode is found to decrease with temperature; such anomalous behavior is driven entirely by electron-phonon interactions, and does not appear in the nearly degenerate infrared-active E(1u) mode. In graphene, the phonon anharmonic lifetimes and decay channels of the A(1)' mode at K dominate over E(2g) at Gamma and couple strongly with acoustic phonons, highlighting how ballistic transport in carbon-based interconnects requires careful engineering of phonon decays and thermalization.