非表示:
キーワード:
-
要旨:
The FK506-binding protein 51 (FICBP51) is a promising drug target for
the treatment of stress-related psychiatric or metabolic disorders. Just
recently, the first selective ligands for FKBP51 were reported based on
an induced fit mechanism, but they are too large for a further drug
development process. We therefore designed and synthesized a novel
series of selective ligands to explore the requirements necessary for
binding to the induced-fit conformation. All ligands of this series show
no binding toward the structurally very similar antitarget FKBP52. With
the cocrystal structure of the best ligand in this novel series we
confirmed the induced fit mechanism. Furthermore, the structure affinity
relationship provides information about beneficial structural features,
which is valuable for the development of improved FKBP51-directed drugs.
