The Scaffold Design of Trivalent Chelator Heads Dictates Affinity and Stability for Labeling His-tagged Proteins in vitro and in Cells

Angewandte Chemie
Karl GatterdamR Tampé

Abstract

Small chemical/biological interaction pairs are at the forefront in tracing protein function and interaction at high signal-to-background ratios in cellular pathways. However, the optimal design of scaffold, linker, and chelator head still deserve systematic investigation to achieve the highest affinity and kinetic stability for in vitro and especially cellular applications. We report on a library of N-nitrilotriacetic acid (NTA)-based multivalent chelator heads (MCHs) built on linear, cyclic, and dendritic scaffolds and compare these with regard to their binding affinity and stability for the labeling of cellular His-tagged proteins. Furthermore, we describe a new approach for tracing cellular target proteins at picomolar probe concentrations in cells. Finally, we outline fundamental differences between the MCH scaffolds and define a cyclic trisNTA chelator that displays the highest affinity and kinetic stability of all reported reversible, low-molecular-weight interaction pairs.

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Citations

Jan 24, 2019·Organic & Biomolecular Chemistry·Michael Rosholm MortensenKurt Vesterager Gothelf
Mar 29, 2019·Angewandte Chemie·Ralph Wieneke, Robert Tampé
Apr 11, 2019·Molecular Biology of the Cell·Tim N BalderingMike Heilemann
Mar 22, 2020·Communications Biology·Stefan BrüchertRobert Tampé
Dec 15, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Li-Song ZhangZhi-Song Zhang
Jan 12, 2021·Chemical Communications : Chem Comm·Joydev HataiDavid Margulies
Feb 27, 2021·Science·M Florencia SánchezRobert Tampé
Jun 1, 2019·Nature Reviews. Chemistry·Cynthia L Schreiber, Bradley D Smith
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ohad SussDavid Margulies

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