STRUCTURE BASED DESIGN OF ANTI-INFECTIVE DRUGS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The discovery and development of new anti-infective drugs is urgently needed, as drug-resistant bacterial and viral diseases become an increasingly serious world health problem. The bacterial ribosome is a primary target of aminoglycoside antibiotics designed to combat bacterial infection. For instance, antibiotics such as paromomycin and tobramycin bind to the RNA aminoacyl decoding site (A-site) within the 16S ribosomal subunit and interfere with translation by inducing miscoding during the protein synthesis, which in turn leads to the death of the bacterial cell. The detailed high-resolution crystal structures of the A-site RNA and other bacterial ribosomal RNA drug targets will allow the elucidation of the interactions between the RNA target and these antibiotics, and will facilitate the structure-based design of novel antibiotics.