Heparin compostions and selectin inhibition

Abstract

The disclosure provides in vitro and in vivo methods for identifying Heparins and Heparinoids that modulate the activity of selectins . The disclosure also provides Heparins and Heparinoids that modulate the activity of selectins . The identification and isolation of these heparin formulations has the potential to mediate a wide variety of pathologies mediated by P- and / or L-selectin, including hematogenous metastasis, diseases associated with inflammation (e.g., asthma, arthritis, allergic dermatitis), ischemia-reperfusion injury, or other pathologies such as sickle cell anemia. Selectin inhibition can be achieved at plasma concentrations lower than those that cause excessive anticoagulation or unwanted bleeding in a human subject.

Description

[0001] Related Application Cross Reference [0002] This application claims priority over US Provisional Application Serial No. 60 / 701,893, filed July 22, 2005, the disclosure of which is incorporated herein by reference. [0003] Statement Regarding Federally Funded Research [0004] This invention was made in part by grant number R01CA38701 awarded by the National Institutes of Health. The government may have certain rights in this invention. technical field [0005] The present invention relates generally to molecular biology, and more particularly to identifying and / or isolating compounds that block L-selectin and / or P-selectin binding activity and attenuate selectin-mediated transfer or other selectin-mediated A method of inducing a heparin variant for a disease or disorder. Background technique [0006] P- and L-selectins are C-type lectins that recognize sialylated, fucosylated, sulfated ligands. P-selectin is stored in resting platelets and endothelial cells a...

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However, human experiments using vitamin K antagonists as an alternative mode of anticoagulation showed no effect on survival in most cancers

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