Mateja Klika Skopic; Christian Gramse; Rosario Oliva; Sabrina Pospich; Laura Neukirch; Magiliny Manisegaran; Stefan Raunser; Roland Winter; Ralf Weberskirch; Andreas Brunschweiger
Chem. Eur. J., 2021, 27(39), 10048-10057
https://doi.org/10.1002/chem.202100980

Abstract

The development of DNA‐compatible reaction methodologies is a central theme to advance DNA‐encoded screening library technology. Recently, we could show that sulfonic acid functionalized block copolymer micelles facilitated Brønsted acid promoted reactions such as the Povarov reaction on DNA‐coupled starting materials with minimal DNA degradation. Here, we investigated the impact of polymer composition on micelle shape, and reaction conversion. A dozen sulfonic acid‐functionalized block copolymers of different molar mass and composition were prepared by RAFT‐polymerization and were tested in the Povarov reaction, removal of the Boc protective group, and the Biginelli reaction. The results showed trends of polymer structure ‐ micellar catalytic activity relationship. For instance, micelles composed of block copolymers with shorter acrylate ester chains formed smaller particles and tended to provide faster reaction kinetics. Moreover, fluorescence quenching experiments as well as circular dichroism spectroscopy showed that DNA‐oligomer‐conjugates, although highly water‐soluble, accumulated very effectively in the micellar compartments as an essential prerequisite for carrying out a DNA‐encoded reaction in the presence of polymer micelles.