Wei-ping Hu,Guo-dong Cao,Jin-hua Zhu,Jia-zhong Li,Xiu-hua Liu
Batatasins are endogenous plant hormones found in yams and other related plant species. These plants are widely consumed as botanical dietary supplements in many parts of the world. This study investigated the inhibitory effects and mechanisms of Batatasin I, III, IV, V against α-glucosidase regarding their antidiabetic activities. The results revealed that Batatasin I, III, IV inhibited α-glucosidase in a reversible and noncompetitive manner, with IC50 values of 2.55, 1.89 and 2.52 mM respectively, while Batatasin V completely abolished its inhibitory activity even at the highest concentrations tested. Furthermore, a class of Batatasin-derived compounds with different substitution patterns was synthesized and subjected to the assay to clarify the structure–activity relationships, which suggested that the hydroxyl at the C-2′ position may play a significant role in improving the inhibitory activities. Their probable binding modes and the specificity of the binding sites were studied using molecule docking simulation. It was concluded that Batatasins, especially Batatasin III and IV, are promising α-glucosidase inhibitors, which therefore could be used as functional food to alleviate postprandial hyperglycemia and as potential candidates for the development of antidiabetic agents.
Quantifying the binding kinetics and affinities of protein–small molecule interactions is critical for biomarker validation, drug discovery, and deep understanding of various biological processes at the molecular-scale. Novel approaches are demanded as most common label-free techniques are mass-sensitive, which are not suitable for the detection of small molecule interactions. Here, an optical imaging platform is developed to measure the binding kinetics of both protein–small molecules and protein–ions based on monolayer MoS 2 , an ultra-thin 2D material whose optical absorption is extremely sensitive to charge. A model is established to calibrate the optical response due to the charged analyte binding and it is applied to quantify the interactions between abl1 kinase and different small-molecule inhibitors. Such a presented method is capable of distinguishing different inhibitors binding to a wild or mutated kinase, which provides guidance for drug evaluation and drug mechanism exploration. The binding kinetics of calcium ions to calmodulin is also measured, further broadening the application field of the method. In addition, the imaging capability allows mapping the local binding kinetics of the molecular interactions with a high resolution, which reveals visible spatial variability and offers a promising tool for studying heterogeneous local interfacial interactions.
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