Fragment merging – and flipping – on the leucine zipper of MITF

Transcription factors can be difficult drug targets, particularly those whose primary structure is a “leucine zipper” in which two α-helices gently coil around each other. Their three-dimensional structure provides few pockets suitable for binding small molecules. In a new (open-access) paper in Nat. Commun., Deborah Castelletti, Wolfgang Jahnke, and a large group of multinational collaborators at Novartis and elsewhere present progress toward one of these, microphthalmia-associated transcription factor (MITF)...