A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway.

CD4(+)CD25(+) regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro.

Tetrahydrochromenoimidazoles as potassium-competitive acid blockers (P-CABs): structure-activity relationship of their antisecretory properties and their affinity toward the hERG channel.

Potassium-competitive acid blockers (P-CABs) constitute a new therapeutic option for the treatment of acid-related diseases that are widespread and constitute a significant economical burden. Enantiomerically pure tetrahydrochromenoimidazoles were prepared using the readily available candidate 4 (BYK 405879) as starting material or the Noyori asymmetric reduction of ketones as key reaction. A comprehensive SAR regarding the influence of the 5-carboxamide and the 8-aryl residue on in vitro activity, acid-suppression in the Ghosh Schild rat, and affinity toward the hERG channel was established.

Recombinant protein expression by targeting pre-selected chromosomal loci.

Background: Recombinant protein expression in mammalian cells is mostly achieved by stable integration of transgenes into the chromosomal DNA of established cell lines. The chromosomal surroundings have strong influences on the expression of transgenes. The exploitation of defined loci by targeting expression constructs with different regulatory elements is an approach to design high level expression systems.

Synthesis and evaluation of 7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridines as potassium-competitive acid blockers.

7H-8,9-Dihydropyrano[2,3-c]imidazo[1,2-a]pyridines with excellent physicochemical and pharmacological properties were identified that represent interesting candidates for further development as potassium-competitive acid blockers (P-CABs). The title compounds were prepared following synthetic pathways that relied either on a Claisen rearrangement/cross-metathesis reaction or on the (asymmetric) reduction of prochiral ketones. The influence of the character of the substituents R3, R6, and Ar on the biological activity and the physicochemical properties of the target compounds was examined.

AggA is required for aggregation and increased biofilm formation of a hyper-aggregating mutant of Shewanella oneidensis MR-1.

Shewanella oneidensis COAG, a hyper-aggregating mutant of MR-1, was isolated from a rifampicin-challenged culture. Compared to the wild-type, COAG exhibited increased biofilm formation on glass carrier material. The role of surface-located proteins in the process of COAG auto-aggregation was confirmed by different proteolytic treatments of the aggregates.