Sequence-specific DNA labelling for fluorescence microscopy.

The preservation of nucleus structure during microscopy imaging is a top priority for understanding chromatin organization, genome dynamics, and gene expression regulation. In this review, we summarize the sequence-specific DNA labelling methods that can be used for imaging in fixed and/or living cells without harsh treatment and DNA denaturation: (i) hairpin polyamides, (ii) triplex-forming oligonucleotides, (iii) dCas9 proteins, (iv) transcription activator-like effectors (TALEs) and (v) DNA methyltransferases (MTases). All these techniques are capable of identifying repetitive DNA loci and robust probes are available for telomeres and centromeres, but visualizing single-copy sequences is still challenging. In our futuristic vision, we see gradual replacement of the historically important fluorescence in situ hybridization (FISH) by less invasive and non-destructive methods compatible with live cell imaging. Combined with super-resolution fluorescence microscopy, these methods will open the possibility to look into unperturbed structure and dynamics of chromatin in living cells, tissues and whole organisms.

Sulfonamide derivatives as multi-target agents for complex diseases.

Sulfonamide derivatives are frequently seen structural motifs in medicinal chemistry. Almost a century after Gerhard Domagk's pioneering work leading to the first sulfonamide antibiotic Prontosil, sulfa-drugs are still widely utilized in various pharmaceutical applications due to their antibacterial, antiviral, antimalarial, antifungal, anticancer, antidepressant, or other properties. In the past few years, the interest in sulfonamides has increased as their broad range of bioactivity and versatile structure make them excellent candidates for repurposing old drugs or developing new multi-target agents in the emerging field of polypharmacology. This digest aims to provide an overview of recent advances in sulfonamide-based bioactive compounds, their importance in drug discovery and development emphasizing multi-target approaches for complex diseases, and their novel contribution to contemporary medicinal chemistry.