Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase

摘要: Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules mediate tumor interactions with platelets, leukocytes, the endothelium. Heparanase an endoglycosidase degrades heparan sulfate in microenvironment, surfaces, vessel wall. Acting together, these facilitate arrest, extravasation, metastasis. Here, we report preparation novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed selectin inhibitory activity. The P-selectin specificity STMC was defined by anomeric linkage C-C bond. This hexasaccharide effective inhibitor vivo. We show selective inhibition attenuates metastasis B16-BL6 melanoma cells, expressing high levels this endoglycosidase, but has no effect on MC-38 carcinoma cells express little or P-selectin-specific attenuated animal models, indicating interaction endothelium critical dissemination. Thus, small size, stability bond, chemically structure newly generated STMCs make them superior to heparin derivatives signify valuable candidates further evaluation.