Issue 6, 2015

A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity

Abstract

A peptide has been designed so that its chelating affinity for one type of metal ion regulates its affinity for a second, different type of metal ion. The prochelator peptide (PCP), which is a fusion of motifs evocative of calcium loops and zinc fingers, forms a 1 : 2 Zn : peptide complex at pH 7.4 that increases its affinity for Zn2+ ∼3-fold in the presence of Tb3+ (log β2 from 13.8 to 14.3), while the 1 : 1 luminescent complex with Tb3+ is brighter, longer lived, and 20-fold tighter in the presence of Zn2+ (log K from 6.2 to 7.5). This unique example of cooperative, heterometallic allostery in a biologically compatible construct suggests the possibility of designing conditionally active metal-binding agents that could respond to dynamic changes in cellular metal status.

Graphical abstract: A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity

Supplementary files

Article information

Article type
Edge Article
Submitted
16 Feb 2015
Accepted
22 Apr 2015
First published
05 May 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2015,6, 3606-3610

Author version available

A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity

B. Alies, J. D. Wiener and K. J. Franz, Chem. Sci., 2015, 6, 3606 DOI: 10.1039/C5SC00602C

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