Serine proteases play critical roles in many physiological and pathological processes, and are
proven diagnostic and therapeutic targets in a number of clinical indications. Suppression of the aberrant
proteolytic activities of these proteases has been clinically used for the treatments of relevant diseases.
Polypeptides with 10-20 residues are of great interests as medicinal modulators of serine proteases,
because these peptides demonstrate the characteristics of both small molecule drugs and macromolecular
drugs. In this review, we summarized the recent development of peptide-based inhibitors
against serine proteases with potent inhibitory and high specificity comparable to monoclonal antibodies.
In addition, we also discussed the strategies of enhancing plasma half-life and bioavailability of
peptides in vivo, which is the main hurdle that limits the clinical translation of peptide-based drugs.
This review advocates new avenue for the development of effective serine protease inhibitors and highlights
the prospect of the medicinal use of these inhibitors.
Keywords: Serine proteases, peptide-based inhibitors, rational design, direct evolution, cancer, thrombosis, crystallography.
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