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.

Aiming to improve binding of porphyrin diphenyl guanidinium conjugates to guanine-quadruplexes: When size matters.

Aiming to improve the binding to Guanine quadruplexes of different topologies, docking studies of porphyrin diphenyl guanidine conjugates previously prepared with an O or a S bridge between the diphenyl moiety and a newly design derivative with an SO2 bridge were carried out using different guanine quadruplexes of different topologies (four parallel, one antiparallel and one hybrid). Positive results were obtained from these computational studies drove us to prepare the SO2 bridge conjugate improving the synthetic route previously reported by us. Biophysical experiments such as UV-thermal melting and circular dichroism indicated the lack of binding to the double stranded DNA and poor binding of the new derivative prepared to any of the guanine quadruplexes studied. These results show that the size of this SO2 bridge could be responsible of the poor experimental binding to guanine quadruplexes.