High Affinity Fluorescent Probe for Proteinase-Activated Receptor 2 (PAR2).

ABSTRACT: PAR2 is a proteolytically activated G protein-coupled receptor (GPCR) that is implicated in various cancers and inflammatory diseases. Ligands with low nanomolar affinity for PAR2 have been developed, but there is a paucity of research on the development of PAR2-targeting imaging probes. Here, we report the development of seven novel PAR2-targeting compounds. Four of these compounds are highly potent and selective PAR2-targeting peptides (EC₅₀ = 10 to 23 nM) that have a primary amine handle available for facile conjugation to various imaging components. We describe a peptide of the sequence Isox-Cha-Chg-ARK(Sulfo-Cy5)-NH₂ as the most potent and highest affinity PAR2-selective fluorescent probe reported to date (EC₅₀ = 16 nM, K _D = 38 nM).

SUBMITTER: LeSarge JC 

PROVIDER: S-EPMC6627725 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature