Investigating Ugi/Passerini Multicomponent Reactions for the Site-Selective Conjugation of Native Trastuzumab**

Site-selective modification of proteins has been the object of intense studies over the past decades, especially in the therapeutic field. Prominent results have been obtained with recombinant proteins, for which site-specific conjugation is made possible by the incorporation of particular amino acid residues or peptide sequences. In parallel, methods for the site-selective and site-specific conjugation of native and natural proteins are starting to thrive, allowing the controlled functionalization of various types of amino acid residues. Pursuing the efforts in this field, we planned to develop a new type of site-selective method, aiming at the simultaneous conjugation of two amino acid residues. We reasoned that this should give higher chances of developing a site-selective strategy compared to the great majority of existing methods that solely target a single residue. We opted for the Ugi four-centre three-component reaction to implement this idea, with the aim of conjugating the side-chain amine and carboxylate groups of two neighbouring lysine and aspartate/glutamate. Herein, we show that this strategy can give access to valuable antibody conjugates bearing several different payloads; furthermore, the approach limits the potential conjugation sites to only six on the model antibody trastuzumab.     

Exploration of chiral Lewis acid Mg2+ catalysts in the synthesis of aryl organophosphate triesters from phosphorus oxychloride through a three-step,two-pot substitution sequence

A variety of nucleophilic and Lewis acid catalysts were examined for use in promoting the synthesis of organophosphate triesters. Eight novel organophosphate triesters are reported here for the first time. MgSO₄ was discovered as an inexpensive catalyst capable of improving the synthesis of a variety of aryl organophosphate triesters from the readily available and low cost precursor phosphorus oxychloride in a three-step, two-pot sequence. Yields for this method improve upon the uncatalyzed method by 8–36%. Several chiral catalysts were tested, but none were able to induce enantioselectivity in the reaction.     

Magnetic breakdown in the electron-doped cuprate superconductor Nd(2-x)Ce(x)CuO4: the reconstructed Fermi surface survives in the strongly overdoped regime

We report on semiclassical angle-dependent magnetoresistance oscillations and the Shubnikov-de Haas effect in the electron-overdoped cuprate superconductor Nd(2-x)CexCuO4. Our data provide convincing evidence for magnetic breakdown in the system. This shows that a reconstructed multiply connected Fermi surface persists, at least at strong magnetic fields, up to the highest doping level of the superconducting regime.     

Perisylvian white matter connectivity in the human right hemisphere

Background  

By using diffusion tensor magnetic resonance imaging (DTI) and subsequent tractography, a perisylvian language network in the human left hemisphere recently has been identified connecting Brocas's and Wernicke's areas directly (arcuate fasciculus) and indirectly by a pathway through the inferior parietal cortex.     

Nachweis und Bestimmung des Natriums

Ohne Zusammenfassung     

Oxygen isotope effect in the ab-plane reflectance of underdoped YBa(2)Cu(3)O(7-delta)

We have measured the effect of oxygen isotope substitution on the ab-plane reflectance of underdoped YBa(2)Cu(3)O(7-delta). The frequency shift of the transverse optic phonons due to the substitution of 16O by 18O yields an isotope effect of the expected magnitude for copper-oxygen stretching modes with alpha=0.5+/-0.1. The reflectance shoulder at 400-500 cm(-1) shows a much smaller exponent of alpha=0.1+/-0.1 in the normal state and alpha=0.23+/-0.1 in the superconducting state. These observations suggest that the shoulder is of electronic origin and not due to a phonon mode as has been suggested recently.     

Halogen Dance on 2-Iodobenzofuran and 2-Iodobenzothiophene and Related Reactions

When 2-iodobenzofuran was treated sequentially with lithium 2,2,6,6-tetramethylpiperidide in tetrahydrofuran at −50 °C and an aldehyde, the 2-substituted 3-iodobenzofuran resulting from the halogen dance was the only isolated product. However, from 2-iodobenzothiophene, these conditions led to mixtures in which the 2-substituted 3-iodobenzothiophene was always accompanied by the 2-substituted benzothiophene. The use of 2-bromobenzothiophene as a catalyst made it possible to significantly reduce this competitive dehalogenation. To confirm the halogen dance reaction, the products were unambiguously synthesized by using direct halogenations and deprotolithiation-trapping sequences as key steps. Our efforts to access 2,7-disubstituted and 7-substituted derivatives of benzofuran and benzothiophene have also been reported.