Methods and compositions for the treatment of β-thalassemia

摘要

Methods and compositions for the treatment of β-thalassemia are provided. Methods and compositions restore or increase erythrocyte maturation in individuals afflicted with β-TM by preventing proteolysis of GATA-1 protein. Screening methods for identifying agents which bind heat shock protein 70 (HSP-70) and inhibit HSP-70 α-globin binding, but which allow GATA-1 protein-HSP-1 binding in a manner that prevents GATA-1 proteolysis.

主权项

1. A method of screening candidate compounds in order to select compounds which inhibit binding of α globin to Hsp70 but which do not inhibit binding of Hsp70 to GATA-1, comprising
i) providing a plurality of candidate compounds which may inhibit binding of α globin to Hsp70; ii) exposing Hsp70 to said plurality of candidate compounds in the presence of α globin and under conditions which allow α globin to bind to Hsp70; iii) identifying Hsp-70-compound complexes which do not contain bound α globin; iv) exposing Hsp-70-compound complexes identified in said identifying step iii) to GATA-1 under conditions that permit Hsp70 to bind to GATA-1; v) identifying Hsp70-compound-GATA-1 complexes fowled in said exposing step iv); and vi) selecting compounds identified in said identifying step v) as compounds which inhibit binding of α globin to Hsp70 but which do not inhibit binding of Hsp70 to GATA-1.