Emerging Targeting Concepts Membrane-Associated Protein Thiol-Disulfide Interchange Activity: A Potential Target for Anti-Viral and Anti-Tumor Drug Design

Abstract

Protein thiol-disulfide oxidoreductive activity is present in most mammalian tissues, functioning as a promoter of thiol-disulfide interchange reactions as indicated by the reactivation of denatured proteins through the rearrangement of mismatched disulfide bonds [1]. Physiologically, the thiol-disulfide interchange reaction is important for protein biosynthesis, especially of proteins destined for secretion [2]. It has also been postulated that the thiol disulfide interchange reaction plays an important role in other cellular functions, such as cell enlargement or the budding of vesicles from membranes, that require the displacement and rearrangement of membrane components [3]. Besides the effects on protein folding and membrane structure, protein thiol-sulfide interchange activity at cell membrane is also known to play an important role in cell death, cell infection, and embryonic development [4]. Many other potential effects of plasma membrane-associated oxidoreductive activity on cellular physiology, including cell differentiation and endocytosis, have recently been suggested [3,4].