Serine Protease Inhibitors and their Therapeutic Applications

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Background

Serine proteases account for more than one-third of proteolytic enzymes. Their name originates from the nucleophilic Ser in the enzyme active site, which attacks the carbonyl moiety of substrate peptide bonds. They are ubiquitous in both eukaryotes and prokaryotes, exerting their proteolytic activities at various levels, and are responsible for the coordination of many physiological functions including immunity, cell cycle, coagulation, digestion, and reproduction. Furthermore, serine proteases are key elements of the inflammation response as they are released from activated leukocytes and mast cells, or generated through the coagulation cascade. In the body, their proteolytic activity is subject to strict regulation by endogenous inhibitors responsible for reducing their catalytic activity when it is no longer necessary. This regulation makes it possible to preserve the homeostasis of the numerous systems in which serine proteases are involved. 

The serine proteases are considered nowadays to be important signaling molecules, and thus their dysregulation is associated with many pathologies ranging from cardiovascular and inflammatory disorders to cancer and neurological pathologies. In light of this, they represent an attractive biological target for the design of bioactive molecules able to modulate their activity. Although many peptides/peptidomimetics, natural products, and small-organic molecules are reported in the literature as potent serine protease inhibitors, the identification of selective inhibitors is still a challenge in medicinal chemistry. Therefore, starting from the results of the most recent literature, it is of great interest to design and synthesize potent inhibitors, paying particular attention to the selectivity, to be developed in vivo animal models. 

The aim of the current Research Topic is to bring together a number of manuscripts reporting original design and synthesis of protease inhibitors. Molecular modeling studies and possible in vitro and/or in vivo studies are also encouraged. Areas to be covered in this Research Topic may include (but are not limited to):

 • Design, synthesis, and optimization of novel serine protease inhibitors and their development as potential drugs  
 • Chemical modification/manipulation of known serine protease inhibitors to improve the understanding of structure-activity relationships (SAR) 
 • New pharmaceutical applications of serine protease inhibitors  

The types of manuscripts welcomed are Original Research, Mini Review (max 1), and Perspective (max 1). Papers reporting molecular docking studies with no experimental validation are not in scope for this collection.

Keywords: Serine proteases, inhibitors, drug design, organic synthesis, inflammatory diseases, respiratory medicine, cancer

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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