Solid-phase synthesis of a library constructed of aromatic phosphate, longalkyl chains and tryptophane components, and identification of potent dipeptide telomerase inhibitors

Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently. we have found novel inhibitors based on the bisindol e skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryp tophane components, from which a D,D-ditryptophane derivative has been iden tified as a new potent telomerase inhibitor with IC50 values of 0.3 muM. A hypothetical binding model for the new inhibitors has been proposed based o n the structure-activity relationship. (C) 2001 Elsevier science Ltd. All r ights reserved.