《Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells》 was written by Horton, Timothy M.; Allegretti, Paul A.; Lee, Sooyeon; Moeller, Hannah P.; Smith, Mark; Annes, Justin P.. Electric Literature of C12H13N3This research focused onzinc DYRK1A insulin pharmacophore pancreatic beta cell; chelation; diabetes; islet; targeted compound delivery; targeting; tissue selectivity; zinc; β cell; β-cell regeneration; β-cell-replication. The article conveys some information:
Diabetes is a hyperglycemic condition characterized by pancreatic β-cell dysfunction and depletion. Whereas methods for monitoring β-cell function in vivo exist, methods to deliver therapeutics to β cells are lacking. We leveraged the rare ability of β cells to concentrate zinc to preferentially trap zinc-binding mols. within β cells, resulting in β-cell-targeted compound delivery. We determined that zinc-rich β cells and islets preferentially accumulated TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline) in a zinc-dependent manner compared with exocrine pancreas. Next, we asked whether appending a zinc-chelating moiety onto a β-cell replication-inducing compound was sufficient to confer preferential β-cell accumulation and activity. Indeed, the hybrid compound preferentially accumulated within rodent and human islets in a zinc-dependent manner and increased the selectivity of replication-promoting activity toward β cells. These data resolve the fundamental question of whether intracellular accumulation of zinc-chelating compounds is influenced by zinc content. Furthermore, application of this principle yielded a proof-of-concept method for β-cell-targeted drug delivery and bioactivity. The experimental part of the paper was very detailed, including the reaction process of Bis(pyridin-2-ylmethyl)amine(cas: 1539-42-0Electric Literature of C12H13N3)
Bis(pyridin-2-ylmethyl)amine(cas: 1539-42-0) is a secondary amine with two picolyl substituents. The compound is a tridentate ligand in coordination chemistry and commonly used to produce Zn-based chemosensors/probes, such as Zinpry.Electric Literature of C12H13N3