Zyn-Linkertm/Heparin Conjugate to Prevent Restenosis

RISK ASSESSMENT FOR CHRONIC HEART DISEASE (CHD) USES INDIRECT ESTIMATES OF LDL CHOLESTEROL FROM TOTAL CHOLESTEROL, HDL AND VLDL ESTIMATES. NO CLINICAL ASSAY EXISTS TO QUANTITATE LDL DIRECTLY FROM SERUM. WE WILL USE A MODEL LDL DETERMINATION ASSAY USING PKH26-ZYN-LINKER LABELLED LDL PARTICLES (LDLS) TO QUANTIFY LDLS DIRECTLY RATHER THAN USING TRADITIONAL PRECIPITATION TYPE ASSAYS AND CALCULATED LDL VALUES. PHASE I'S SPECIFIC AIMS ARE: 1) COMPARISON OF PKH26 ZYN-LINKER LDLS TO COMMERICALLY AVAILABLE LDLS USING PHYSICAL PROPERTIES SUCH AS DENSITY, STABILITY, DYE TO PARTICLE RATIOS AND FUNCTIONAL PROPERTIES (E.G. LDL RECEPTOR BINDING); 2) GENERATION OF SOLID SUBSTRATES SPECIFICALLY ABLE TO REACT WITH NORMAL AND MUTANT LDL PARTICLES; AND 3) CREATION OF A MODEL ASSAY TO DIRECTLY MEASURE LDL CONCENTRATIONS. THE ASSAY WILL BE BASED UPON COMPETITIVE BINDING OF PATIENT LDLS WITH REAGENT PARTICLES AND SIGNALS WILL BE DETECTED USING SPECTROFLUOROMETRIC METHODS.