TY - CHAP
T1 - Serpins
T2 - Development for therapeutic applications
AU - Lucas, Alexandra
AU - Yaron, Jordan R.
AU - Zhang, Liqiang
AU - Macaulay, Colin
AU - McFadden, Douglas
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Serine protease inhibitors, or serpins, function as central regulators for many vital processes in the mammalian body, maintaining homeostasis for clot formation and breakdown, immune responses, lung function, and hormone or central nervous system activity, among many others. When serine protease activity or serpin-mediated regulation becomes unbalanced or dysfunctional, then severe disease states and pathogenesis can ensue. With serpinopathies, genetic mutations lead to inactive serpins or protein aggregation with loss of function. With other disorders, such as sepsis, atherosclerosis, cancer, obesity, and the metabolic syndrome, the thrombotic and thrombolytic cascades and/or inflammatory responses become unbalanced, with excess bleeding and clotting and upregulation of adverse immune responses. Returning overall balance can be engineered through introduction of a beneficial serpin replacement as a therapeutic or through blockade of serpins that are detrimental. Several drugs have been developed and are currently in use and/or in development both to replace dysfunctional serpins and to block adverse effects induced by aberrant protease or serpin actions. With this chapter, we provide a general overview of the development of a virus-derived serpin, Serp-1, and serpin reactive center loop (RCL) peptides, as therapeutics. Serp-1 is a virus-derived serpin developed as a new class of immune modulator. We will use the development of Serp-1 as a general introduction to serpin-based drug development.
AB - Serine protease inhibitors, or serpins, function as central regulators for many vital processes in the mammalian body, maintaining homeostasis for clot formation and breakdown, immune responses, lung function, and hormone or central nervous system activity, among many others. When serine protease activity or serpin-mediated regulation becomes unbalanced or dysfunctional, then severe disease states and pathogenesis can ensue. With serpinopathies, genetic mutations lead to inactive serpins or protein aggregation with loss of function. With other disorders, such as sepsis, atherosclerosis, cancer, obesity, and the metabolic syndrome, the thrombotic and thrombolytic cascades and/or inflammatory responses become unbalanced, with excess bleeding and clotting and upregulation of adverse immune responses. Returning overall balance can be engineered through introduction of a beneficial serpin replacement as a therapeutic or through blockade of serpins that are detrimental. Several drugs have been developed and are currently in use and/or in development both to replace dysfunctional serpins and to block adverse effects induced by aberrant protease or serpin actions. With this chapter, we provide a general overview of the development of a virus-derived serpin, Serp-1, and serpin reactive center loop (RCL) peptides, as therapeutics. Serp-1 is a virus-derived serpin developed as a new class of immune modulator. We will use the development of Serp-1 as a general introduction to serpin-based drug development.
KW - Clinical trial
KW - Drug development
KW - Peptides
KW - Serine protease inhibitors
KW - Serpins
UR - http://www.scopus.com/inward/record.url?scp=85053084917&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053084917&partnerID=8YFLogxK
U2 - 10.1007/978-1-4939-8645-3_17
DO - 10.1007/978-1-4939-8645-3_17
M3 - Chapter
C2 - 30194606
AN - SCOPUS:85053084917
T3 - Methods in Molecular Biology
SP - 255
EP - 265
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -