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Multivalent chelators for spatially and temporally controlled protein functionalization

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Abstract

Site-specific protein modification—e.g. for immobilization or labelling—is a key prerequisite for numerous bioanalytical applications. Although modification by use of short peptide tags is particularly attractive, efficient and bio-orthogonal systems are still lacking. Here, we review the application of multivalent chelators (MCH) for high-affinity yet reversible recognition of oligohistidine (His)-tagged proteins. MCH are based on multiple nitrilotriacetic acid (NTA) moieties grafted on to molecular scaffolds suitable for conjugation to surfaces, probes or other biomolecules. Reversible interaction with the His-tag is mediated via transition metal ions chelated by the NTA moieties. The small size and biochemical compatibility of these recognition units and the possibility of rapid dissociation of the interaction with His-tagged proteins despite sub-nanomolar binding affinity, enable distinct and versatile handling and modification of recombinant proteins. In this review, we briefly introduce the key principles and features of MCH–His-tag interactions and recapitulate the broad spectrum of bioanalytical applications with a focus on quantitative protein interaction analysis on micro or nano-patterned solid surfaces and specific protein labelling in living cells.

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Acknowledgments

This work is dedicated to Professor Dr Günter Gauglitz on the occasion of his 70th birthday.

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  1. Department of Biology, University of Osnabrück, Barbarastr. 11, 49076, Osnabrück, Germany

    Changjiang You & Jacob Piehler

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  1. Changjiang You
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  2. Jacob Piehler
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Correspondence to Jacob Piehler.

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This paper is dedicated to Professor Günter Gauglitz on the occasion of his 70th birthday.

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You, C., Piehler, J. Multivalent chelators for spatially and temporally controlled protein functionalization. Anal Bioanal Chem 406, 3345–3357 (2014). https://doi.org/10.1007/s00216-014-7803-y

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  • DOI: https://doi.org/10.1007/s00216-014-7803-y

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