Generation and screening of dynamic combinatorial libraries

ORGN 330

Olof Ramstrom, Zhichao Pei, Rikard Larsson, and Magnus Hermansson. Department of Chemistry, Royal Institute of Technology, Teknikringen 56, S-100 44 Stockholm, Sweden
Dynamic combinatorial chemistry (DCC) is a supramolecular concept that extends beyond static combinatorial chemistry towards adaptive chemical systems. The concept relies on reversible reactions or interactions between sets of basic components to generate continually interchanging adducts, giving access to dynamic combinatorial libraries (DCLs) whose constituents are all possible combinations of the components available. It facilitates the rapid generation of libraries and allows for target-driven generation or amplification of the active constituent(s) of the libraries, thus performing a self-screening process by which the active species are preferentially expressed and retrieved from the DCL. In the present study, the implementation of such libraries on biological interactions is illustrated, where dynamic libraries, generated from small arrays of initial precursors, are probed against binding to biological receptors in aqueous media.