Back

Dev P Arya

Dev P Arya

Clemson University, USA

Title: Bacterial ribosome selective aminoglycosides

Biography

Dev Arya earned his B.Sc. (chemistry honors program) from St. Stephen's College, Delhi; and PhD (Bioorganic Chemistry) from Northeastern University, Boston. After spending his postdoctoral years in the labs of Prof. T. C. Bruice (UC Santa Barbara), he joined the faculty at Clemson University. Dr. Arya is a recipient of a National Science Foundation CAREER Award (2002) and the ACS Horace S. Isbell Award of the Division of Carbohydrate Chemistry (2007). He has served as the Program Chair (2004-2008), Chair-Elect (2009-2010) and Chair (2010-2011) of the ACS Division of Carbohydrate Chemistry.

Abstract

Aminoglycosides inhibit bacterial growth by binding to the A-site decoding region of the bacterial 16s ribosomal RNA (rRNA) within the 30S ribosomal subunit. Previous work has shown that there is approximately a five-fold difference in the affinity of neomycin for the human A-site model and the E. coli model. We have developed a screening assay that rapidly identifies compounds that discriminate between the two model rRNA structures. This approach, coupled with a rapid solid phase synthesis method, has identified active aminoglycosides that show large differences in binding affinity for the E. coli A-site and the human A-site than that of neomycin (~30 fold). The methodology for synthesizing, screening for both ribosomal binding/selectivity and bacterial growth inhibition, and rapid analysis of the data provides a systematic method for identification of bacterial ribosome specific antibacterial that can evade bacterial resistance pathways.