In eukaryotic cells, the genomic DNA is hierarchically organized into chromatin. Chromatin structures and dynamics influence all nuclear functions that are guided by DNA, and thus regulate gene expression. Chromatin structure aberrations cause various health issues, such as cancer, lifestyle-related diseases, mental disorders, infertility, congenital diseases, and infectious diseases. Many studies have unveiled the fundamental features and the heterogeneity of the nucleosome, which is the basic repeating unit of chromatin. The nucleosome is the highly conserved primary chromatin architecture in eukaryotes, but it also has structural versatility. Therefore, analyses of these primary chromatin structures will clarify the higher-order chromatin architecture. This review focuses on structural and functional studies of nucleosomes, based on our research accomplishments.

Pradimicins (PRMs) are an exceptional family of natural products that specifically bind d-mannose (Man). In the past decade, their scientific significance has increased greatly, with the emergence of biological roles of Man-containing glycans. However, research into the use of PRMs has been severely limited by their inherent tendency to form water-insoluble aggregates. Recently, we have established a derivatization strategy to suppress PRM aggregation, providing an opportunity for practical application of PRMs in glycobiological research. This article first outlines the challenges in studying Man-binding mechanisms and structural modifications of PRMs, and then describes our approach to address them. We also present our recent attempts toward the development of PRM-based research tools.

The instability of repeat sequences in the human genome results in the onset of many neurological diseases if the repeats expand above a certain threshold. The transcripts containing long repeats sequester RNA binding proteins. The mechanism of repeat instability involves metastable slip-out hairpin DNA structures. Synthetic organic chemists have focused on the development of small organic molecules targeting repeat DNA and RNA sequences to treat neurological diseases with repeat-binding molecules. Our laboratory has studied a series of small molecules binding to mismatched base pairs and found molecules capable of binding CAG repeat DNA, which causes Huntington’s disease upon expansion, CUG repeat RNA, a typical toxic RNA causing myotonic dystrophy type 1, and UGGAA repeat RNA causing spinocerebellar ataxia type 31. These molecules exhibited significant beneficial effects on disease models in vivo, suggesting the possibilities for small molecules as drugs for treating these neurological diseases.