Merging of a Supramolecular Ligand with a Switchable Luminophore - Light-Responsiveness, Photophysics and Bioimaging.

In this contribution we report on a novel approach towards luminescent light-responsive ligands. To this end, cyanostilbene- guanidiniocarbonyl-pyrrole hybrids were designed and investigated. Merging of a luminophore with a supramolecular bioactive ligand bears numerous advantages by overcoming the typical drawbacks of drug-labelling, influencing the overall performance of the active species by attachment of a large luminophore.

Tuning Nanobodies' Bioactivity: Coupling to Ultrasmall Gold Nanoparticles Allows the Intracellular Interference with Survivin.

Nanobodies are highly affine binders, often used to track disease-relevant proteins inside cells. However, they often fail to interfere with pathobiological functions, required for their clinical exploitation. Here, a nanobody targeting the disease-relevant apoptosis inhibitor and mitosis regulator Survivin (SuN) is utilized.

Taspase1 Facilitates Topoisomerase IIβ-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription.

The human protease Taspase1 plays a pivotal role in developmental processes and cancerous diseases by processing critical regulators, such as the leukemia proto-oncoprotein MLL. Despite almost two decades of intense research, Taspase1's biology is, however, still poorly understood, and so far its cellular function was not assigned to a superordinate biological pathway or a specific signaling cascade. Our data, gained by methods such as co-immunoprecipitation, LC-MS/MS and Topoisomerase II DNA cleavage assays, now functionally link Taspase1 and hormone-induced, Topoisomerase IIβ-mediated transient DNA double-strand breaks, leading to active transcription.

Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

Invited for the cover of this issue are Christoph Hirschhäuser and his colleagues from the University of Duisburg-Essen. The image depicts a biotin-labelled transfection vector selectively channelling DNA into a cancer cell. The QR code on the label will lead you to a video abstract (https://youtu.

Advances towards Cell-Specific Gene Transfection: A Small-Molecule Approach Allows Order-of-Magnitude Selectivity.

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small-molecule approach paved the way for precise structure-activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA-binding motif tetralysine-guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR-based optimization.

The Taspase1/Myosin1f-axis regulates filopodia dynamics.

The unique threonine protease Tasp1 impacts not only ordered development and cell proliferation but also pathologies. However, its substrates and the underlying molecular mechanisms remain poorly understood. We demonstrate that the unconventional Myo1f is a Tasp1 substrate and unravel the physiological relevance of this proteolysis.

Cancer-Cell-Specific Drug Delivery by a Tumor-Homing CPP-Gossypol Conjugate Employing a Tracelessly Cleavable Linker.

Tumor-targeted drug delivery is highly important for improving chemotherapy, as it reduces the dose of cytotoxic agents and minimizes the death of healthy tissues. Towards this goal, a conjugate was synthesized of gossypol and a MCF-7 cancer cell specific CPP (cell penetrating peptide), thus providing a selective drug delivery system. Utilizing the aldehyde moiety of gossypol, the tumor homing CPP RLYMRYYSPTTRRYG was attached through a semi-labile imine linker, which was cleaved in a traceless fashion under aqueous conditions and had a half-life of approximately 10 hours.