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Serpins: Development for Therapeutic Applications

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Serpins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1826))

Abstract

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.

Serpins

pervasive in blood

and bone

and brain

Essential to life

and lungs

and flow

When lost

and broken

replace, repair

Life stems

from virus

to man

Alexandra Lucas, 2018

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Author information

Authors and Affiliations

  1. Center for Personalized Diagnostics and Center for Immunotherapy Vaccines and Virotherapy, Biodesign Institute, Arizona State University, 727 E Tyler St, Tempe, AZ, USA

    Alexandra Lucas, Jordan R. Yaron, Liqiang Zhang & Grant McFadden

  2. CGMBio Consulting, TechAlliance of Southwestern Ontario, London, ON, Canada

    Colin Macaulay

Authors
  1. Alexandra Lucas
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  2. Jordan R. Yaron
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  3. Liqiang Zhang
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  4. Colin Macaulay
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  5. Grant McFadden
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Corresponding author

Correspondence to Alexandra Lucas .

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Editors and Affiliations

  1. Biodesign Center for Personalized Diagnostics and Center for Immunotherapy Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA

    Alexandra Lucas

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Lucas, A., Yaron, J.R., Zhang, L., Macaulay, C., McFadden, G. (2018). Serpins: Development for Therapeutic Applications. In: Lucas, A. (eds) Serpins. Methods in Molecular Biology, vol 1826. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8645-3_17

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  • DOI: https://doi.org/10.1007/978-1-4939-8645-3_17

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8644-6

  • Online ISBN: 978-1-4939-8645-3

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