A High-Throughput Fluorescence Polarization-Based Assay for the SH2 Domain of STAT4.

The signal transducer and activation of transcription (STAT) proteins are a family of Src homology 2 (SH2) domain-containing transcription factors. The family member STAT4 is a mediator of IL-12 signalling and has been implicated in the pathogenesis of multiple autoimmune diseases. The activity of STAT4 requires binding of phosphotyrosine-containing motifs to its SH2 domain.

Efficacy and safety at 6 months of the XEN implant for the management of open angle glaucoma.

The purpose of this study is to evaluate the efficacy and complications of the XEN implant as a solo procedure or in association with cataract surgery in patients with open angle glaucoma (OAG). All patients who received a XEN implant between June 2017 and June 2018 were included in the study. The primary and secondary outcomes were: the reduction of the intraocular pressure (IOP) at 6 months postoperatively, the decrease of the glaucoma medications 6 months after surgery, the clinical success rate (eyes (%) achieving ≥20% IOP reduction on the same or fewer medications without secondary surgical intervention), the frequency and type of postoperative interventions as well as the complication rate.

Comparative Effectiveness and Tolerance of Subliminal Subthreshold Transscleral Cyclophotocoagulation With a Duty Factor of 25% Versus 31.3% for Advanced Glaucoma.

Unlabelled: PRéCIS:: Subliminal subthreshold transscleral cyclophotocoagulation (SS-TSCPC) with duty cycles 25% and 31.3% seems to be an effective approach to reduce intraocular pressure (IOP) in glaucoma that is refractory to medical management.

Objective: The objective of this study was to compare the effectiveness and the tolerance of SS-TSCPC with a duty cycle of 25% versus 31.

Argon Laser Iridoplasty For Plateau Iris Syndrome: Long-Term Outcomes of 48 Eyes.

Precis: Argon laser peripheral iridoplasty (ALPI) was performed on 48 eyes with plateau iris syndrome (PIS). Indentation gonioscopy was used to monitor the opening of the iridocorneal angle. Mean intraocular pressure (IOP) at 5 years decreased from 15.

The STAT5b Linker Domain Mediates the Selectivity of Catechol Bisphosphates for STAT5b over STAT5a.

STAT family proteins are important mediators of cell signaling and represent therapeutic targets for the treatment of human diseases. Most STAT inhibitors target the protein-protein interaction domain, the SH2 domain, but specificity for a single STAT protein is often limited. Recently, we developed catechol bisphosphates as the first inhibitors of STAT5b demonstrated to exhibit a high degree of selectivity over the close homologue STAT5a.

Synthesis and biochemical evaluation of highly enantiomerically pure (R,R)- and (S,S)-alexidine.

Alexidine is in everyday human use as oral disinfectant and contact lens disinfectant. It is used as a mixture of stereoisomers. Since all of alexidine's known biological targets are chiral, the biological activity of any of its chiral stereoisomers could be significantly higher than that of the mixture of stereoisomers.

Selective targeting of disease-relevant protein binding domains by O-phosphorylated natural product derivatives.

Phosphorylation-dependent protein binding domains are crucially important for intracellular signaling pathways and thus highly relevant targets in chemical biology. By screening of chemical libraries against 12 structurally diverse phosphorylation-dependent protein binding domains, we have identified fosfosal and dexamethasone-21-phosphate as selective inhibitors of two antitumor targets: the SH2 domain of the transcription factor STAT5b and the substrate-binding domain of the peptidyl-prolyl isomerase Pin1, respectively. Both compounds are phosphate prodrugs with documented clinical use as anti-inflammatory agents in humans and were discovered with a high hit rate from a small subgroup within the screening library.

Phosphopeptides with improved cellular uptake properties as ligands for the polo-box domain of polo-like kinase 1.

Human polo-like kinase 1 (Plk1) is involved in cell proliferation and overexpressed in a broad variety of different cancer types. Due to its crucial role in cancerogenesis Plk1 is a potential target for diagnostic and therapeutic applications. Peptidic ligands can specifically interact with the polo-box domain (PBD) of Plk1, a C-terminal located phosphoepitope binding motif.

A novel direct screening method for alkyl glucoside production by glucosidases expressed in E. coli in 96-well plates.

The present work describes the development of a novel direct screening method, assayed in 96-well format, for evaluation of enzymatic alkyl glycoside production in a hexanol-water two-phase system. Alkyl glycosides are surfactants with a range of applications and with good biodegradability and low toxicity. Enzymatic synthesis makes it possible to prepare beta-d-glucopyranosides with high purity.

Development of high-throughput assays based on fluorescence polarization for inhibitors of the polo-box domains of polo-like kinases 2 and 3.

The serine/threonine kinases Plk1, Plk2, and Plk3 harbor a protein-protein interaction domain dubbed polo-box domain (PBD). Recently, the inhibition of the PBD of the cancer target Plk1 has been successfully explored as an alternative to the inhibition of the kinase by ATP-competitive ligands. However, because the PBDs of Plk1, Plk2, and Plk3 have very similar optimal binding motifs, absolute specificity for the PBD of Plk1 over the PBDs of Plk2 and Plk3 may also represent a big challenge for a small molecule.