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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X-ray crystallography and surface plasmon resonance studies. Importantly, these structural studies also define possible druggable target sites in uPAR for small molecules and provide guidelines for the development of reporter groups applicable for non-invasive molecular imaging of uPAR expression in vivo by positron emission tomography. In this review, we will discuss recent advances in our perception of the structure-function relationships of uPAR ligation and how these may assist translational research in preclinical intervention studies of uPAR function.
OriginalsprogEngelsk
TidsskriftCurrent Drug Targets
Vol/bind12
Udgave nummer12
Sider (fra-til)1711-28
Antal sider18
ISSN1389-4501
DOI
StatusUdgivet - 2011

ID: 33274246