PROSPECTIVE BROAD-SPECTRUM ANTIBACTERIAL AGENT

BASED ON WORK PUBLISHED IN 1981 BY JAYARAMAN, MCPARLAND, MILLER, AND TS'O (PNAS 78 1537 (1981) WE PROPOSE THAT A NOVEL TYPE OF ULTRA-BROAD-SPECTRUM ANTIBACTERIAL AGENT MAY BE POSSIBLE. SUCH AN AGENT WOULD BIND TO A KEY RNA SEQUENCEWHICH IS EXPECTED TO BE HYPERSENSITIVE TO INACTIVATION ONLY IN PROCARYOTES. IF SUCH AN ANTIBACTERIAL AGENT PROVES FEASIBLE THEN THE BASIC APPROACH MAY ALSO ALLOW RATIONAL DESIGN OF BROAD-SPECTRUM AGENTS EFFECTIVE AGAINST OTHER CLASSES OF PATHOGENS - INCLUDING PARTICULARLY FUNGI. HEREIN WE PROPOSE TO PREPARE A VARIETY OF UNCHARGED STEREOREGULAR SEQUENCE-SPECIFIC NUCLEIC BINDING AGENTS TARGETED AGAINST THE SHINE-DALGARANO CONSENUS SEQUENCE OF PROCARYOTIC MRNA'S AND AGAINST ITS COMPLEMENTARY SEQUENCE IN BSCTERIAL 16S RRNA. SPECIAL MODIFICATIONS WILL BE INCORPORATED TO VARY THEIR TARGET BINDING AFFINITIES OVER A BROAD RANGE. THESE SUBSTANCES WILL BE ASSESSED IN BOTH BACTERIA AND ANIMAL CELLS FOR INHIBITION OF PROTEIN SYNTHESIS AND EFFECT ON CELL GROWTH AND DIVISION.