Powered by OpenAIRE graph
Found an issue? Give us feedback
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Imperial College Lon...arrow_drop_down
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
https://dx.doi.org/10.25560/89...
Other literature type . 2019
License: CC BY NC
Data sources: Datacite
versions View all 2 versions
addClaim

Luminescent compounds for targeting formyl peptide receptors

Authors: Boltersdorf, Tamara;

Luminescent compounds for targeting formyl peptide receptors

Abstract

Unregulated inflammation is implicated in a variety of disease states such as stroke, cancer and neurodegenerative conditions and often the extent of inflammatory response can determine the prognosis for a particular disease state. Human neutrophils express formyl peptide receptors one (FPR1) and two (FPR2/ALX, also known as the lipoxin A4 receptor) and are known to both drive vascular inflammation and at the same time be involved in its resolution. Therefore, these receptors represent an attractive target for non-invasive visualisation of inflammation in disease states. The work within this thesis focusses on designing luminescent imaging probes that selectively tag neutrophils in an inflammatory context. To achieve this, a small-molecule FPR2/ALX ligand was chosen based on ease of synthesis, ability for further functionalisation and a dose-dependent neutrophil response observed in vitro. The targeting system was initially combined with a rhodamine-based dye and binding via the neutrophil FPR family was confirmed via pharmacological blocking. In vitro, the probe did not affect neutrophil responses and in vivo preferential uptake by neutrophils in a model of acute inflammation compared to control groups was demonstrated. Via minor synthetic alterations, a pH-responsive version based on the rhodamine spirocyclisation equilibrium was prepared (pKcycl = 3.97) and the compound was shown to be fluorescent in stimulated neutrophils in vitro but remained non-fluorescent under normal physiological conditions. By appending the same targeting group to metal chelates, compounds with long-lived luminescence signals that can be separated from cellular autofluorescence via lifetimes, were prepared. Time-resolved microscopy on activated and unactivated human neutrophils incubated with FPR2/ALX-targeted lanthanide-based compounds was performed, but high concentrations were required. A second iteration of probe design, using a Re(I) tricarbonyl motif, resulted in time-resolved images of neutrophils at lower probe concentration. Finally, a construct containing a lanthanide unit, a pH-responsive fluorophore and the targeting group was formed and the energy transfer processes in the Tb(III) analogue were investigated. The observed energy transfer provides a unique opportunity to enhance emission properties of the compound for time-resolved imaging via donor-sensitised, long-lived emission, providing an alternative radiative pathway that circumvents the formally forbidden, characteristically weak lanthanide emission.

Country
United Kingdom
Related Organizations
Keywords

540

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    0
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
Powered by OpenAIRE graph
Found an issue? Give us feedback
selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
Green
Related to Research communities
Cancer Research