Granzymes as Potential Targets for Rational Drug Design

Abstract

A family of serine proteases, the granzymes, found in the dense cytoplasmic granules of lymphocytes/granulocytes have become targets of interest for rational drug design because of their role in cell-mediated cytotoxicity. Granzymes represent potential late-stage, specific targets for immunomodulation with the promise of fewer side-effects than agents acting at earlier stages of the immune response, such as cyclosporine A (Neoral®, Sandimmune®) and tacrolimus/FK-506 (Prograf®). Recent reports suggesting other possible biological roles for granzymes, including antigen processing and lymphocyte recruitment, and the increasing evidence for the involvement of aspartic acid-specific proteases, such as granzyme B and the interleukin converting enzyme (ICE), in apoptosis or programmed cell death pathways have increased the interest in this growing family of enzymes. This review summarizes current progress in granzyme research and outlines some of the prospects for future work in this area.