SCREENING CHEMICAL LIBRARIES FOR NUCLEIC-ACID-BINDING DRUGS BY IN-VITRO SELECTION - A TEST-CASE WITH LIVIDOMYCIN

Screening new drugs is a costly and time-consuming process. Identifyin g new targets for existing therapeutics is often a particularly effect ive avenue for drug development. We have investigated whether in vitro selection can be used for target acquisition. Aminoglycoside antibiot ics are known to bind to and inactivate functional natural nucleic aci ds, such as ribosomal RNA. As an example of how new targets for aminog lycosides could be identified, a lividomycin aptamer was iteratively i solated from a random sequence pool. The consensus sequence of this an d other anti-aminoglycoside aptamers was used as the basis for a compr ehensive search of natural sequence databases. Surprisingly, a high de gree of similarity was found between aptamers and genomic sequences fr om a variety of organisms. While many of the similarities found are in regions of unknown or nonessential function, some of the sequences ar e found in critical genes in pathogenic organisms.