SYNTHESIS AND TESTING OF ANTIBIOTIC ANTISENSE CONJUGATES

THE MAJOR GOAL OF THIS PROJECT IS TO PRODUCE ANTISENSE-OLIGODEOXYNUCLEOTIDES THAT WILL READILY BE TAKEN UP BY TARGET CELLS. TO ACCOMPLISH THIS, WE WILL ATTACH ANTIBIOTICS TO ANTISENSE-OLIGODEOXYNUCLEOTIDES UTILIZING NOVEL TECHNOLOGIES. THE ANTIBIOTICS TO BE EMPLOYED ARE READILY TAKEN UP BY EUKARYOTIC CELLS AND SHOULD ACT AS PERMEATION ENHANCERS FOR THE OLIGODEOXYNUCLEOTIDES. ANTIBIOTICS HAVE BEEN CHOSEN, BECAUSE IN ADDITION TO THEIR UPTAKE BY CELLS, THEY ARE FDA APPROVED DRUGS; SAFE FOR USE IN HUMANS. THEY ARE NOT READILY METABOLIZED BY EUKARYOTES AND THUS SHOULD FORM STABLE CONJUGATES. THE CRITERIA FOR SUCCESSFUL CONJUGATES WILL BE INHIBITION OF PROTEIN SYNTHESIS OF TARGET MRNA, INCREASED UPTAKE INTO CELLS, AND RELATIVE EASE OF SYNTHESIS. IF THESE CRITERIA ARE MET, ANTIBIOTIC-OLIGODEOXYNUCLEOTIDE CONJUGATES WILL HAVE GREAT POTENTIAL IN THE ANTISENSE OLIGODEOXYNUCLEOTIDE FIELD OF DRUG THERAPY, ESPECIALLY IN THE AREA OF ANTIVIRAL DRUGS. ONE OF THE MAJOR PROBLEMS FACING THIS AREA TODAY IS THE EFFICIENT UPTAKE OF ANTISENSE OLIGODOTIDES INTO EUKARYOTIC CELLS. THE CONJUGATES SHOULD MINIMIZE THIS SITUATION. THE INNOVATIVE TECHNOLOGY DEVELOPED FROM THIS PROJECT WILL BE APPLICABLE TO THE ATTACHMENT OF OTHER TYPES OF MOLECULES TO ANTISENSE OLIGODEOXYNUCLEOTIDES.