Biologic conjugates that have anti-inflammatory properties and can be used as systemic agents for treatment of blood clots, stroke, heart attack, or other inflammatory/prothrombotic conditions.
- Can also be used to coat cells and tissues to enhance their anti-inflammatory properties or can be used to coat devices such as vascular grafts, stents, heart valves, dialysis membranes, membrane oxygenators, catheters, or guide wires to alter surface properties.
- Has dramatically enhanced water solubility, improved plasma half-life, increased stability, and possibly decreased protein immunogenicity due to addition of poly(ethylene glycol).
An effective blood-contacting surface is dependent upon the presence of physiologically relevant anti-thrombotic mechanisms that are incorporated into the engineered blood-material interface. Thrombomodulin (TM) is a critical regulator of the protein C pathway, which represents the major anticoagulant mechanism operative in both normal and injured blood vessels under physiologic conditions in vivo. Although TM can be incorporated into engineered blood-contacting surfaces, major drawbacks of using full length TM include loss of stability with time and significant reduction in TM bioactivity as a result of surface coupling methods currently available. Dr. Chaikof and colleagues have developed novel compositions and a method for adding poly(ethylene glycol) to produce improved thrombomodulin derivatives. These TM derivatives can also be conjugated to linear or multifunctional natural or synthetic compounds that contain other anti-inflammatory or anti-thrombotic properties. Use of these TM derivatives in combination with other anti-inflammatory and/or anti-thrombotic agents may improve biocompatibility and reduce host immune response following cell/organ transplantation or implantation of prosthetic devices.
Biologic conjugates have been synthesized and described. Conjugates retain full bioactivity.
Publication: Bioconjugate Chem. 2004, 15, 1005-1007.