SYNTHESIS AND ANALYSIS OF 506BD, A HIGH-AFFINITY LIGAND FOR THE IMMUNOPHILIN FKBP

The design, synthesis, and analysis of a high-affinity ligand, 506BD, for the human immunophilin FKBP is described. The synthesis illustrates a novel hydroboration reaction that proceeds with unusual regio- and stereochemical control. In accord with expectations regarding the structural requirements for FKBP binding, 506BD potently inhibits the rotamase activity of FKBP (inhibitory constant K(i) = 5 nM). The significance of these and other findings with regard to a biological model for immunophilin-ligand actions is described.