Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function.

Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.

[Bitterness of the mixture of clarithromycin dry syrup and carbocisteine preparation--difference between brand name and generic drugs].

The purpose of this study was to assess the bitterness intensity and pH of the solutions of clarithromycin dry syrup (CAM-DS), carbocisteine preparation (CC), and the concomitant use of both drugs. We conducted 6 types of human gustatory sensation tests with 6 healthy male volunteers. As a result, there was almost no difference in the bitterness intensity of CAM-DS between the branded (the latest and former preparations) and the generic formulations. The bitterness intensity of CAM-DS (the latest and former preparations of the branded as well as the generic formulations) was almost equally enhanced by mixing it with either the branded CC-DS or the branded and the generic carbocisteine granule (CC-Gr). On this occasion, the enhancing the bitterness of the branded CAM-DS (latest and former preparation) was nearly avoided safely by dosage form's changing CC-DS or CC-Gr to the branded CC-Sy. However, unlike the branded CC-Sy, some generic CC-Sy failed to suppress the bitterness. Furthermore, it was proven that some generic CAM-DS were shown to exhibit bitterness when mixed with even branded CC-Sy. In conclusion, it should be noted that the extent of bitterness of the mixture of CAM-DS and CC highly varies among the generic formulations.