Navigation

0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via
4.4 Selections of DNA-Encoded Libraries to Protein Targets within Living Cells

DOI: 10.1055/sos-SD-241-00252

Cai, B.; Krusemark, C. J.Science of Synthesis: DNA-Encoded Libraries, (20241607.

General Introduction

While DNA-encoded libraries (DELs) now play an important role in drug discovery, selections of DELs have been largely limited to biochemically pure proteins that are immobilized on solid supports. As the concentration of active protein is the driver for ligand binding, high protein purity and activity are critical parameters in DEL selections. Unfortunately, many sought-after drug targets cannot be purified or reconstituted biochemically, which excludes them from the traditional DEL approach.[‌1‌] Additionally, even in best-case scenarios, significant time and effort in a DEL campaign is devoted to protein production and quality control. Performing DEL selections against protein targets within live cells would be desirable and remove the requirement of prior protein purification.[‌2‌,‌3‌] This would allow assessment of ligand binding to target proteins within a more native environment, where post-translational modifications and endogenous binding partners can be preserved.[‌4‌] Furthermore, selections against intracellular proteins, rather than stand-alone protein targets, may be more likely to generate effective lead compounds that retain activity in vivo.[‌5‌]

Me eeeeeee MMM eeeeeeeeee eeeeee eeee eeeee, e eeeeeeeeeee eeeeeeeee eeee ee eee eeeeeeee eeeeeeeeeeeeee ee MMM-eeeeee eeeee eeeeeeeee. Meeeee eeeeee ee eeeeeeeeee eeeeeee eeeee eeee eeee eeeee eeeeeee eeeeee eeeeeeeeeeeeee eee eeeeeee eeeeeeeee eeeeee eeeeeeeeee. Me eeeeeeee eeeee eeeeee, ee eeee e eeeeee eeee-eeeeeeeeeee eeeeeee (eMMM88)[‌8‌] ee eeeeeee MMM eeeeee eee eeee eeeeeeee. eMMMe eeee eeeeeeeeee eeeee ee eeeeeee eeeeeee, eeeeeeeee eeeeeee eeeee eee eeeeeee–eeeeeee eeee eeeeeeeee,[‌8‌] eeee eeee eeeee eeee eeee eeeeeeeee eeeeee eeeeeeeeee. Mee eeeeeee eeeee eeee e eeeeeee ee eeeeeeeeeeee eeeeeeeee eeeeeeeeeeee eeeeeeee eeee eeeeeeeeeeee. Me eeeee ee eeeeee eeeeeee eeee eee-eeeeeee eeeeee eeee eeeee, ee eeee eeeeeeee eeeeeeeeeeee ee eeee eeeeeee–eeeeee eeeeeee eeeeeeeeeeee eeeee ee eeeeeeeeeeee ee eee eeeeeee eeeeee,[‌8‌] eee eeeeeee eeeeeeeee eeeeeee eeeeeeeeee ee eeeeee eee-eeeeeee. Meeeeee eeeee eee eeeeeeee eeeeeeeeeeee-eeeee eeeeeeee ee eeeeeee eeee-eeee MMM eeeeeeeeee, eeeeeeeeee ee MMMe eeeeeee eeeeeeeeeeeee eeeeeee eeeeeee eeee eeee eeeeeeee ee eeeeee eeeeeeeeeeeeee ee e MMM eee eee eeeeeeee eMMM ee eee eeeeeee eeeeee eeee e eeee eeeeee.[‌8‌] Meeee ee eeeeeeee eeeeeeee eeeeeeeeeeee eeeeeeeeee eee MMM eeeeeeeeee ee eeeee eeeee e eMMM eee e eeeeeeee eeeeeeeeeeee-eeeee eeeeeeee (Meeeee 8).

Meeeee 8 Meeeeeeeeeee Meeeeeee ee Meee-Meee MMM Meeeeeeeee[‌8‌]

M eeeeeee eeeeee eeee e eeeeeeeeeeee eee ee eeeeeeeee ee MMM888 eeeeeeeeee eeeee. Meee eeeeeeeee eeeeeeee ee e MMM eeeeeee ee eMMM88, eee eeeeeee eeeee eeeee eeeee eeeeeee e eeeeeee eee e MMM-eeeeee eeeeee, eeeee eeeeeee e eeeeeeee eeee ee ee eeeeee eeeeeee eee eeeeeee eee MMM ee eeeeeeee eeeeeeee. Meeee eeeee ee eee eeeee, eeeeeee eeeeeee eee eeeeeeeeee eeeeeeee ee eeeee eee eee MeeeMee (MM) eeeeee. Meeeeeeee eee eeeeeee-eeeeeeeeee eeeeee eee eeeeeee ee eeeeee eee-eeeeeee; eeeeeeee eeeeeee eee eeeeeeeeee ee MMM eeeeeeeeee.

References


Cookie-Einstellungen