We report a high-affinity photoswitchable DNA binder, which displays different nucleosome-binding capacities upon visible-light irradiation.

Transgene expression of green fluorescent protein (GFP) has facilitated the spatiotemporal investigation of host-pathogen interactions; however, introduction of the GFP gene remains challenging in drug-resistant bacteria. Herein, we report a novel far-red fluorescent nucleic acid stain, 6-TramTO-3, which efficiently labels bacteria through a DNA binding mode without affecting growth and viability. Exemplarily, we stained Klebsiella pneumoniae, a major threat to hospitalized patients, and deciphered divergent interaction strategies of antibiotic-resistant and antibiotic-sensitive Klebsiella strains with immune cells. 6-TramTO-3 constitutes an off-the-shelf reagent for real-time analysis of bacterial infection, including strains for which the use of genetically encoded reporters is not feasible. Eventually, our approach may aid the development of strategies to combat a major worldwide health threat: multidrug-resistant bacteria.

The complexity of the world's current grand challenges demands interdisciplinary approaches. The education of future scientists must cross the silos of the traditional disciplines; however, there is still a strong reluctance to tear such walls down. Here, we describe an integrative chemical biology course focused on epigenetics that strives to bring research culture to chemistry and biology Master's students. The course, which has been successfully implemented for the past two years, combines three modules: lectures, discovery-based research lab, and science communication. Importantly, the outline of our course design could be easily adapted to different fields, improving the synergy between research and teaching in our universities.

DNA-binding polyamides are synthetic oligomers of pyrrole/imidazole units with high specificity and affinity for double-stranded DNA. To increase their synthetic diversity, we report a mild methodology based on 4-methyltrityl (Mtt) solid phase peptide synthesis (SPPS), whose building blocks are more accessible than the standard Fmoc and Boc SPPS ones. We demonstrate the robustness of the approach by preparing and studying a hairpin with all precursors. Importantly, our strategy is orthogonal and compatible with sensitive molecules and could be readily automated.

Background Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy (PDT) might be beneficial. Therefore, a combination of the photosensitizer hypericin (HYP) with HIPEC was evaluated in an animal model. Procedure An established HIPEC animal model for rhabdomyosarcoma (NOD/LtSz‐scid IL2Rγnullmice, n = 80) was used. All groups received HYP (100 μg/200 μl) intraperitoneally with and without cisplatin‐based (30 or 60 mg/m2) HIPEC (37°C or 42°C, for 60 minutes) (five groups, each n = 16). Peritoneal cancer index (PCI) was documented visually and by HYP‐based photodynamic diagnosis (PDD). HYP‐based PDT of the tumor was performed. Tissue samples were evaluated regarding proliferation (Ki‐67) and apoptosis (TUNEL). Results HYP uptake was detected even in smallest tumor nodes (<1 mm) with improved tumor detection during PDD (PCI with PDD vs. PCI without PDD: 8.5 vs. 7, p < .001***). Apoptotic effects after PDT without HIPEC were limited to the tumor surface, whereas PDT after HIPEC (60 mg/m2, 42°C) showed additional reduction of tumor proliferation in the top nine to 11 cell layers (50 μm). Conclusion HYP as fluorescent photosensitizer offers an intraoperative diagnostic advantage detecting intraperitoneal tumor dissemination. The combination of HYP and cisplatin‐based HIPEC was feasible in vivo, showing enhanced effects on tumor proliferation and apoptosis induction across the tumor surface. Further studies combining HYP and HIPEC will follow to establish a clinical application.