In this article, we examine the docking of 10 analytes on the Whelk-O1 stationary phase. A proper representation of analyte flexibility is essential in the docking analysis, and analyte force fields have been developed from a series of B3LYP calculations. Molecular dynamics simulations of a representative Whelk-O1 interface, in the presence of racemic analyte and solvent, form the basis of the analysis of chiral selectivity. The most probable docking arrangements are identified, the energy changes upon docking are evaluated, and separation factors are predicted. From comparisons between the analytes, the mechanism of chiral selectivity is divided into contributions from hydrogen bonding, ring-ring interactions, steric hindrance, and molecular flexibility. We find that both hydrogen bonding and ring-ring interactions are necessary to localize the analyte within the Whelk-O1 cleft region. We also identify one docking mechanism that is often dominant and analyze the conditions that lead to alternate docking modes.

ABSTRACT. Osteosarcoma (OS) is an aggressive cancer of the long bones, and usually affects children and young adults. The receptor for advanced glycation end-products (RAGE) has recently been recognized as an oncogenic receptor that binds to different ligands, and promotes the progression of various cancers. However, little is known about the association between RAGE and the pathogenesis of OS. In this study, we first examined the expression of RAGE in OS tissues using immunohistochemical staining, western blotting, and reverse transcription quantitative polymerase chain reaction. We then determined the influence of the overexpressed RAGE on the proliferation of U-2OS cells in vitro. The results showed that RAGE was overexpressed in OS tissues compared with peritumor tissues, at both the mRNA and protein levels, and there was a significant association between overexpressed RAGE and clinicopathological characteristics, such as clinical stage and distant metastasis. Moreover, the overexpression of RAGE in U-2OS cells significantly promoted their proliferation in vitro. In conclusion, this study indicated that RAGE is overexpressed in OS tissue and promotes the proliferation of U-2OS cells. These data imply that RAGE promotes the growth of OS, and is a potential diagnostic biomarker and therapeutic target for the disorder.

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