Serpins: Development for therapeutic applications

Alexandra Lucas, Jordan R. Yaron, Liqiang Zhang, Colin Macaulay, Douglas McFadden

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages255-265
Number of pages11
DOIs
StatePublished - Jan 1 2018

Publication series

NameMethods in Molecular Biology
Volume1826
ISSN (Print)1064-3745

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Keywords

  • Clinical trial
  • Drug development
  • Peptides
  • Serine protease inhibitors
  • Serpins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Lucas, A., Yaron, J. R., Zhang, L., Macaulay, C., & McFadden, D. (2018). Serpins: Development for therapeutic applications. In Methods in Molecular Biology (pp. 255-265). (Methods in Molecular Biology; Vol. 1826). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-8645-3_17