Selectin Targetting Bioconjugates

Stephen Massia (Inventor)

Research output: Patent

Abstract

The present invention relates to the sythesis of bioconjugates to be utilized as a therapeutic agent. More specifically, it relates to bioconjugates as a class of anti-inflammatory/immuno-suppresent thereapeutics that slectively target and locally bind to inflamed tissue surfaces forming a protective colloid barrier against pathologically driven excessive leukocyte adhesion/infilitration and subsequent tissue injury. Although leukocyte adhesion to tissue surfaces is essential for normal immune system function, leukocyte/tissue adhesion plays a major role in a number of pathological processes including septic shock, post-trauma multiple organ failure, ischemic reperfusion injury, transplant rejection, inflammatory diseases, and autoimmune diseases. therefore the current invention could be exploited as a systemically delierable therapy that selectively and locally targets leukocyte-adhesive tissues to suppress pathologically excessive leukocyte-mediated damage to healthy tissues and thus limit deleterious outcomes.The selectin family includes molecules that contain N-terminal domain homologous to lectins. They are Ca 2+ dependent transmembrane glycoproteins that bind to sialylated carbohydrate moiteies present on target proteins. There are three different selectins: P-, E-, and L-selectin, and the type of cell on which it is predominently expressed gives this naming convention. The primary functions of slectins are lymphocyte homing and leukocyte recruitment to inflamed tissue.E- and P-selectin expressed on the surface of endothalial cells loosely tethers circulating leukocytes, this will lead to leukocyte rolling along the vessel wall. Leukocyte rolling crucial in bringing leukocytes to a site of inflammation where strong interactions involving ICAM-1 and other cell adhesion molecules and specifically bind to selectins. It has been found that in many cases, binding to selectins greatly reduces the inflammatory response.
Original languageEnglish (US)
StatePublished - Jul 6 2004

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