HIGHER-ORDER IMINODIACETIC ACID LIBRARIES FOR PROBING PROTEIN-PROTEININTERACTIONS

Full details of the preparation of iminodiacetic acid diamide dimer (2 040 compounds), trimer (560 compounds), and tetramer (1596 compounds) libraries by multistep convergent solution-phase synthesis for studyin g protein-protein interactions are provided. The libraries were assemb led in a format providing small 8-10 compound mixtures and the deconvo lution of many of the small mixtures to identify screening leads by re synthesis of the individual components have been conducted for 320 of the individual compounds to date. A representative example of the subs equent exploration of the structure-activity relationships for an iden tified receptor binding antagonist (200 additional individual compound s) and steps taken for potential elaboration to a receptor dimerizatio n agonist are defined with preparation of representative linked dimers (70 compounds). (C) 1998 Elsevier Science Ltd. All rights reserved.