Peptide Mimetic Drugs for Modulating Thrombosis and Hemostasis

Abstract

Preclinical Research Hemostasis is the complex physiological process that stems bleeding at an injury site while simultaneously maintaining unobstructed circulation in other areas of the body. This system is kept in balance with finely tuned regulation by pro- and antithrombotic agents. When this balance is thrown out of equilibrium, uncontrolled bleeding, or thrombotic complications can occur. Because of the high number of hemostatic disorders, researchers are continually searching for improved technologies for controlling coagulation. Recently, peptide mimetic strategies have been employed to target and regulate various stages of the coagulation cascade. In this review, we present an overview of the coagulation cascade and provide a summary of various peptide-mimetic approaches for its modulation. Drug Dev Res 78 : 236-244, 2017. © 2017 Wiley Periodicals, Inc.

Sulfotyrosine residues: Interaction specificity determinants for extracellular protein–protein interactions

“…Aberrant hemostasis—ranging from profuse bleeding to excessive clotting—underlies or complicates several human conditions, and many treatments have been developed ( 134 , 135 , 136 ). The serine endoprotease α-thrombin is central to controlling the balance between initiating and terminating blood clotting (thrombosis).…”

State-of-the-art review - A review on snake venom-derived antithrombotics: Potential therapeutics for COVID-19-associated thrombosis?

“…A small peptide that has been designed to mimic a particular region of a protein or enzyme yet displays its biological function is known as a peptidomimetic. Several of such peptidomimetic inhibitors that target blood coagulation factors and platelet receptors or regulate various stages of the coagulation cascade to produce an antithrombotic effect have been projected as drug prototypes to treat thrombotic disorders [155] , [156] , [157] , [158] . The peptidomimetics of a small stretch of snake venom toxins that target and inhibit the function of blood coagulation factors and/or platelet receptors [136] will be a unique approach for inventing improved antithrombotic drug prototypes to treat coagulation disorders in COVID-19.…”

Sulfotyrosine, an interaction specificity determinant for extracellular protein-protein interactions

“…The third sequence group (Fig. 2C Aberrant hemostasis -ranging from profuse bleeding to excessive clotting -underlies or complicates several medical conditions, and many treatments have been developed (106)(107)(108). Hirudin, a clot-inhibiting therapeutic used for over one hundred years, is an sTyr-containing direct thrombin inhibitor (DTI) made by Hirudo leeches (17,109,110).…”

“…Aberrant hemostasis -ranging from profuse bleeding to excessive clotting -underlies or complicates several human conditions, and many treatments have been developed (134)(135)(136). The serine endoprotease a-thrombin is central to controlling the balance between initiating and terminating blood clotting (thrombosis).…”