Predicting efficiency of NECEEM-based partitioning of protein binders from nonbinders in DNA-encoded libraries

Electrophoresis
Sven KochmannSergey N Krylov

Abstract

Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) is an affinity method for separating binder-target complexes from nonbinders by gel-free CE. NECEEM is a promising high-efficiency method for partitioning protein binders from nonbinders in DNA-encoded libraries (DEL), such binders are used as "hits" in drug development. It is important to be able to predict the efficiency of NECEEM-based partitioning, which is the efficiency of collecting binders while removing nonbinders for a specific protein and a specific DEL with a minimum of empirical information. Here, we derive and study the dependence of efficiency of NECEEM-based partitioning on electrophoretic mobilities of the protein and the DNA moiety in DEL compounds. Our derivation is based upon a previously found relation between the electrophoretic mobility of protein-binder complex and measured electrophoretic mobilities of the protein and unbound DEL and their estimated sizes. The derivation utilizes the assumption of Gaussian shapes of electrophoretic peaks and the approximation of the efficiency of partitioning by the background of nonbinders - a fraction of nonbinders, which elutes along with protein-binder complexes. Our results will serve as a gu...Continue Reading

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Citations

May 22, 2019·Expert Opinion on Drug Discovery·Guixian ZhaoXiaoyu Li
Dec 5, 2020·Future Medicinal Chemistry·Daniel ConoleMichael J Waring
Apr 24, 2021·Chembiochem : a European Journal of Chemical Biology·Yiran Huang, Xiaoyu Li
Nov 9, 2019·Analytical Chemistry·Courtney J KristoffLisa A Holland
Feb 6, 2022·Nature Chemistry·Yiran HuangXiaoyu Li

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