STRUCTURE-BASED DESIGN OF INHIBITORS OF PURINE NUCLEOSIDE PHOSPHORYLASE

Inhibitors of purine nucleoside phosphorylase may have therapeutic val ue in the treatment of T-cell proliferative diseases such as T-cell le ukemia, in the suppression of host-versus-graft response in organ tran splants, and in the treatment of T-cell-mediated autoimmune diseases. Competitive inhibitors of this enzyme have been designed using the thr ee-dimensional structure of the enzyme determined by X-ray crystallogr aphy. This approach has resulted in the synthesis of the most potent a nd membrane-permeable inhibitors of purine nucleoside phosphorylase re ported so far.