Structure-based design of inhibitors of purine nucleoside phosphorylase.

Abstract

Inhibitors of purine nucleoside phosphorylase may have therapeutic value in the treatment of T-cell proliferative diseases such as T-cell leukemia, in the suppression of host-versus-graft response in organ transplants, and in the treatment of T-cell-mediated autoimmune diseases. Competitive inhibitors of this enzyme have been designed using the three-dimensional structure of the enzyme determined by X-ray crystallography. This approach has resulted in the synthesis of the most potent and membrane-permeable inhibitors of purine nucleoside phosphorylase reported so far.