Synthetic Combinatorial Libraries as an Alternative Strategy for the Development of Novel Treatments for Infectious Diseases

Abstract

Synthetic combinatorial chemistry approaches have created a vast new source of molecular diversity for the potential identification of lead compounds. This revolutionary field enables hundreds to thousands times more compounds to be synthesized and screened in shorter periods of time relative to traditional approaches. Synthetic combinatorial libraries (SCLs) have been used in laboratories to develop antimicrobial and antifungal compounds, as well as novel treatments for HIV infection. Deconvolution procedures are an essential element in the identification of active individual compounds from mixture-based libraries. The positional scanning approach uses a positional scanning SCL (PSSCL), in which the key functionalities at each position of the active compound can be determined directly from the library screening data. Thus, a PS-SCL is composed of sublibraries, each addressing a single position of the sequence while representing the same collection of individual compounds. When used in concert, the data derived from each sublibrary yields information about the key functionalities for each position. Mixture-based PS-SCLs therefore, have the advantage of greatly decreasing the economics and time constraints of single compound array systems.