NEW COUPLING GROUPS FOR AQUEOUS IMMOBILIZATION CHEMISTRY

THE LONG-TERM OBJECTIVE OF THIS PROJECT IS THE DEVELOPMENT OF NEW REAGENTS AND METHODOLOGIES FOR COUPLING POLYMERS AND ANTITHROMBOGENIC COMPOUNDS TO POLYMER SURFACES IN MULTISTEP SEQUENCES UNDER AQUEOUS CONDITIONS. THE SPECIFIC AIMS OF THE PHASE I RESEARCH ARE: (1) SYNTHESIS, CHARACTERIZATION, AND STABILITY STUDIES OF POLYETHYLENE OXIDE (PEO) SPACERS MODIFIED WITH NOVEL, WATER-STABLE END GROUPS; (2) DEVELOPMENT OF A PROCESS FOR CHEMICALLY TREATING AMINE-FUNCTIONALIZED SILICONE SURFACES WITH THESE WATER-STABLE PEO SPACER MOLECULES UNDER AQUEOUS CONDITIONS; AND (3) DEVELOPMENT OF HIGHLY EFFICIENT PROCEDURES FOR ATTACHMENT OF BIOMOLECULES TO PEO-TREATED SURFACES AND EVALUATION OF BIOACTIVITY. SUCCESSFUL REAGENTS AND METHODOLOGIES WOULD PERMIT THE TREATMENT OF A VARIETY OF COMPLEX, MULTICOMPONENT BLOOD-CONTACTING DEVICES UNDER CONDITIONS THAT WOULD NOT IMPAIR THE CHEMICAL, TOXICOLOGICAL, AND MECHANICAL PERFORMANCE SPECIFICATIONS FOR THESE DEVICES. THESE RESULTSWOULD BE IMMEDIATELY APPLICABLE TO A WIDE VARIETY OF EXISTING FDA-APPROVED BLOOD-CONTACTING DEVICES AND TO MANY APPLICATIONS INVOLVING SOLID-PHASE SYNTHESIS AND PROTEIN AND DRUG CONJUGATION CHEMISTRY.