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Issue 44, 2014
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Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding

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Abstract

The recombinant Kv7.2 calmodulin (CaM) binding site (Q2AB CaMBD) shows a high tendency to aggregate, thus complicating biochemical and structural studies. To facilitate these studies we have conceived bis-PEG-peptide CaMBD-mimetics linking helices A and B in single, easy to handle molecules. Short PEG chains were selected as spacers between the two peptide molecules, and a Cu(I)-catalyzed cycloaddition (CuAAC) protocol was used to assemble the final bis-PEG-peptide conjugate, by the convenient functionalization of PEG arms with azide and alkyne groups. The resulting conjugates, with a certain helical character in TFE solutions (CD), showed nanomolar affinity in a fluorescence CaM binding in vitro assay, higher than just the sum of the precursor PEG-peptide affinities, thus validating our design. The approach to these first described examples of Kv7.2 CaMBD-mimetics could pave the way to chimeric conjugates merging helices A and B from different Kv7 subunits.

Graphical abstract: Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding

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Supplementary files

Article information


Submitted
27 Jun 2014
Accepted
11 Sep 2014
First published
11 Sep 2014

Org. Biomol. Chem., 2014,12, 8877-8887
Article type
Paper
Author version available

Clicked bis-PEG-peptide conjugates for studying calmodulin-Kv7.2 channel binding

M. A. Bonache, A. Alaimo, C. Malo, O. Millet, A. Villarroel and R. González-Muñiz, Org. Biomol. Chem., 2014, 12, 8877
DOI: 10.1039/C4OB01338G

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