Jump to main content
Jump to site search


Structure–activity relationship study of ProxyPhos chemosensors for the detection of proximal phosphorylation and other phosphate species

Author affiliations

Abstract

Chemosensors for the detection of phosphate-containing biological species are in high need. Detection of proximally phosphorylated sites of PPi and those found in peptides and proteins has been demonstrated using chemosensors containing pyrene, as a fluorescent reporter, and a Zn2+-chelate, as a phosphate-binding group. Using these sensors, detection of proximal phosphate groups is afforded by binding of at least two of the sensor molecules to the adjacent phosphates, via the Zn2+ centres, leading to excimer formation between the pyrene groups and the corresponding shift in emission from 376 to 476 nm. Although several reports of this chemosensor class have been made, no detailed studies of selectivity of these sensors among major phosphate targets have been reported. In this study, a library of this class of chemosensors, termed ProxyPhos, which contained various linkers and Zn2+-chelating groups (i.e. DPA, cyclen and cyclam), was prepared and the effects of structural variation on the sensing efficiency and selectivity were evaluated among proximally phosphorylated peptides, proteins, nucleotides, Pi and PPi. As a result of this study, we have identified ProxyPhos library members that are most suitable for the detection of proximally phosphorylated peptides, PPi, UTP, and a DpYD peptide motif, and have generally provided a foundation for the selection of ProxyPhos chemosensors for further development of specific biologically relevant assays. The broad utility of ProxyPhos is further supported by the demonstrated lack of these sensors’ cytotoxicity, ability to rapidly permeate into live and fixed cells and compatibility with gel staining methods.

Graphical abstract: Structure–activity relationship study of ProxyPhos chemosensors for the detection of proximal phosphorylation and other phosphate species

Back to tab navigation

Supplementary files

Publication details

The article was received on 01 May 2017, accepted on 14 Sep 2017 and first published on 14 Sep 2017


Article type: Paper
DOI: 10.1039/C7AN00722A
Citation: Analyst, 2017, Advance Article
  •   Request permissions

    Structure–activity relationship study of ProxyPhos chemosensors for the detection of proximal phosphorylation and other phosphate species

    A. D. Cabral, B. I. Murcar-Evans, K. Toutah, M. Bancerz, D. Rosa, K. Yuen, T. B. Radu, M. Ali, A. Penkul, D. Kraskouskaya and P. T. Gunning, Analyst, 2017, Advance Article , DOI: 10.1039/C7AN00722A

Search articles by author

Spotlight

Advertisements