Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization of proteins

• Published in: Bioorganic & medicinal chemistry Vol. 6; no. 8; pp. 1309 - 1335
• Main Authors: Keenan, Terence, Yaeger, David R., Courage, Nancy L., Rollins, Carl T., Pavone, Mary Ellen, Rivera, Victor M., Yang, Wu, Guo, Tao, Amara, Jane F., Clackson, Tim, Gilman, Michael, Holt, Dennis A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.1998
• Subjects: Apoptosis - drug effects; Carboxylic Acids - chemical synthesis; Carboxylic Acids - pharmacology; Dimerization; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; Humans; Immunophilins - metabolism; In Vitro Techniques; Inhibitory Concentration 50; Ligands; Piperidines - chemical synthesis; Piperidines - pharmacology; Proteins - metabolism; Structure-Activity Relationship; Tacrolimus Binding Proteins; Tumor Cells, Cultured

The total synthesis and in vitro activities of a series of chemical inducers of dimerization (CIDs) is described. The use of small-molecule CIDs to control the dimerization of engineered FKBP12-containing fusion proteins has been demonstrated to have broad utility in biological research as well as p...