Synthesis and Screening of a DNA‐Encoded Library of Non‐Peptidic Macrocycles**
Eric Koesema, Animesh Roy, Nicholas G. Paciaroni, Carlos Coito, Michal Tokmina‐Roszyk, Thomas Kodadek
Abstract
There is considerable interest in the development of libraries of non-peptidic macrocycles as a source of ligands for difficult targets. We report here the solid-phase synthesis of a DNA-encoded library of several hundred thousand thioether-linked macrocycles. The library was designed to be highly diverse with respect to backbone scaffold diversity and to minimize the number of amide N-H bonds, which compromise cell permeability. The utility of the library as a source of protein ligands is demonstrated through the isolation of compounds that bind Streptavidin, a model target, with high affinity.
Topics & Concepts
DNACombinatorial chemistryComputational biologyChemistryComputer scienceStereochemistryBiologyBiochemistryChemical Synthesis and AnalysisMonoclonal and Polyclonal Antibodies ResearchClick Chemistry and Applications