Photoswitchable Probes of Oxytocin and Vasopressin

Oxytocin (OT) and vasopressin (VP) are related neuropeptides
that
regulate many biological processes. In humans, OT and VP act via four
G protein-coupled receptors, OTR, V1aR, V1bR,
and V2R (VPRs), which are associated with several disorders.
To investigate the therapeutic potential of these receptors, particularly
in the receptor-dense areas of the brain, molecular probes with a
high temporal and spatial resolution are required. Such a spatiotemporal
resolution can be achieved by incorporating photochromic moieties
into OT and VP. Here, we report the design, synthesis, and (photo)pharmacological
characterization of 12 OT- and VP-derived photoprobes using different
modification strategies. Despite OT’s and VP’s sensitivity
toward structural changes, we identified two photoprobes with good
potency and photoswitch window for investigating the OTR and V1bR. These photoprobes should be of high value for producing
cutting-edge photocontrollable peptide probes for the study of dynamic
and kinetic receptor activation processes in specific regions of the
brain.