Preface [Hot Topic: Bioorganic Chemical Approaches for the Design of Protease Inhibitors (Guest Editor: Dong H. Kim)]

Proteases play crucial roles for the normal functioning of biological systems. Proteins that are generated in ribosome must be degraded in order for them to carry out their functions in the biological systems and these protein degradations are catalyzed by a variety of proteolytic enzymes. A myriad of metabolic reactions involved in diverse physiological processes such as protein turnover, digestion, blood coagulation and wound healing, fertilization, cell differentiation and growth, immune response, and apoptosis are effected and controlled by proteases. Uncontrolled, unregulated or undesired proteolyses cause aberrant physiological processes, leading to many disease states such as emphysema, viral infection, stroke, cancer, Alzheimer's disease, inflammation, and arthritis. Inhibitors of proteases thus have potential utility for therapeutic intervention in a variety of disease states, and in fact numerous protease inhibitors are currently being used as clinical agents for treatment of a variety of states. The proteolytic enzymes can be divided into four major classes on the basis of the mode of their catalytic actions: serine-, cysteine-, aspartic- and metallo-proteases. In this special issue, recent developments in design protocols of small molecule inhibitors that are effective against these enzymes have been reviewed by leading scientists in their respective field. The review by Zhang and Groutas focuses the design of mechanism-based and alternate substrate inhibitors of serine proteases, and Kim reviewes recent progresses on the design of irreversible inhibitors that covalently modify carboxypeptidase A, a protopytical zinc proteases. Mobsahery and associates derscribe the design strategy for a novel type of irreversible inhibitors for matrix metalloproteases (MMPs), which show an excellent selectivity toward specific MMPs. In light of the fact that there is mounting evidences that broad-spectrum inhibition of MMPs is highly undesirable due to diverse physiological activities these enzymes manifest, selective inhibition of MMPs is currently of prime concern with regard to obtaining therapeutically viable inhibitors of MMPs. Vederas and collegues report strategies used for designing inhibitors effective against 3C cysteine proteases from picornaviridae, viruses comprising one of the most important families of human pathogens. Since excellent review articles related to aspartic proteases have appeared recently, no inclusion for inhibitors of the enzymes is made in this issue. It is hoped that the present reviews would serve to provide new impetus for efficient design and discovery of new medicinal agents. Finally, I would like to express my sincere thanks to all the contributors, whose hard work and dedication made this special issue possible.