Conformational Changes in DNA upon Ligand Binding Monitored by Circular Dichroism

Circular dichroism (CD) spectroscopy is an optical technique that measures the difference in the absorption of left and right circularly polarized light. This technique has been widely employed in the studies of nucleic acids structures and the use of it to monitor conformational polymorphism of DNA has grown tremendously in the past few decades. DNA may undergo conformational changes to B-form, A-form, Z-form, quadruplexes, triplexes and other structures as a result of the binding process to different compounds. Here we review the recent CD spectroscopic studies of the induction of DNA conformational changes by different ligands, which includes metal derivative complex of aureolic family drugs, actinomycin D, neomycin, cisplatin, and polyamine. It is clear that CD spectroscopy is extremely sensitive and relatively inexpensive, as compared with other techniques. These studies show that CD spectroscopy is a powerful technique to monitor DNA conformational changes resulting from drug binding and also shows its potential to be a drug-screening platform in the future

Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats

Akram Hossain,1,2 Fuminori Yamaguchi,1 Kayoko Hirose,1 Toru Matsunaga,3 Li Sui,1 Yuko Hirata,1 Chisato Noguchi,1 Ayako Katagi,1 Kazuyo Kamitori,1 Youyi Dong,1 Ikuko Tsukamoto,4 Masaaki Tokuda11Department of Cell Physiology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan; 2Research and Development, Matsutani Chemical Industry Co., Ltd., Kitaitami, Itami-shi, Hyogo, Japan; 3Division of Hospital Pathology, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, Japan; 4Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Ikenobe, Miki, Kagawa, JapanBackground: The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, D-psicose (D-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects.Aim: Above mentioned efficacy of D-psicose (D-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of D-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats.Methods: Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests.Results: D-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue.Conclusion: Our findings suggest that the rare sugar D-psicose could be beneficial for the prevention and control of obesity and hyperglycemia with the preservation of β-cells in the progression of T2DM.Keywords: rare sugar d-psicose, OLETF rats, type 2 diabetes mellitus, insulin resistance, adiposity, β-islet preservatio

Looped out and perpendicular: Deformation of Watson–Crick base pair associated with actinomycin D binding

Many anticancer drugs interact directly with DNA to exert their biological functions. To date, all noncovalent, intercalating drugs interact with DNA exclusively by inserting their chromophores into base steps to form elongated and unwound duplex structures without disrupting the flanking base pairs. By using actinomycin D (ActD)-5′-GXC/CYG-5′ complexes as examples, we have found a rather unusual interaction mode for the intercalated drug; the central Watson–Crick X/Y base pairs are looped out and displaced by the ActD chromophore. The looped-out bases are not disordered but interact perpendicularly with the base/chromophore and form specific H bonds with DNA. Such a complex structure provides intriguing insights into how ligand interacts with DNA and enlarges the repertoires for sequence-specific DNA recognition