STRUCTURE OF ACRIDINIUM ESTER-LABELED PROBES

THE AIM OF THIS PROJECT IS TO ELUCIDATE THE STRUCTURAL INTERACTION BETWEEN CONJUGATED CHEMILUMINESCENT ACRIDINIUM ESTERS AND DNA/DNA HYBRIDS. SUCH STRUCTURAL INFORMATION WILL BE OBTAINED USING VARIOUS PHYSICAL AND CHEMICAL METHODS; HOWEVER, A PRIMARY FOCUS IS TO EMPLOY NUCLEAR MAGNETIC RESONANCE TECHNIQUES. THIS INFORMATION WILL SERVE TO OPTIMIZE A HOMOGENOUS DIAGNOSTIC ASSAY METHOD BASED UPON PROTECTION AGAINST DEGRADATION OF A CHEMILUMINESCENT ACRIDINIUM ESTER LABEL. PRELIMINARY EXPERIMENTS INDICATE THAT THE HYDROLYSIS AND SUBSEQUENT CHEMILUMINESCENCE LOSS OF ACRIDINIUM ESTERS ATTACHED TO DNA PROBES IS SIGNIFICANTLY REDUCED WHEN SUCH PROBES ARE HYBRIDIZED COMPARED TO UNHYBRIDIZED PROBES. THE STRUCTURE STUDIES PLANNED HERE WILL PROVIDE THE NECESSARY STRUCTURAL INFORMATION TO MORE FULLY UNDERSTAND THE MECHANISM OF THIS PROTECTION AND WILL PERMIT THE OPTIMIZATION OF THIS UNIQUE HOMOGENEOUS SYSTEM. SUCH OPTIMIZATION WILL ALLOW THE DEVELOPMENT OF A WORKING HOMOGENEOUS ASSAY FORMAT AND WILL CONTRIBUTE SIGNIFICANTLY TO THE SPEED AND SIMPLICITY WITH WHICH INFECTIOUS DISEASES ARE DETECTED.