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Bioportide: an emergent concept of bioactive cell-penetrating peptides

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Abstract

Cell-penetrating peptides (CPPs) have proven utility for the highly efficient intracellular delivery of bioactive cargoes that include peptides, proteins, and oligonucleotides. The many strategies developed to utilize CPPs solely as pharmacokinetic modifiers necessarily requires them to be relatively inert. Moreover, it is feasible to combine one or multiple CPPs with bioactive cargoes either by direct chemical conjugation or, more rarely, as non-covalent complexes. In terms of the message-address hypothesis, this combination of cargo (message) linked to a CPP (address) as a tandem construct conforms to the sychnological organization. More recently, we have introduced the term bioportide to describe monomeric CPPs that are intrinsically bioactive. Herein, we describe the design and biochemical properties of two rhegnylogically organized monometic CPPs that collectively modulate a variety of biological and pathophysiological phenomena. Thus, camptide, a cell-penetrant sequence located within the first intracellular loop of a human calcitonin receptor, regulates cAMP-dependent processes to modulate insulin secretion and viral infectivity. Nosangiotide, a bioportide derived from endothelial nitric oxide synthase, potently inhibits many aspects of the endothelial cell morphology and movement and displays potent anti-angiogenic activity in vivo. We conclude that, due to their capacity to translocate and target intracellular signaling events, bioportides represent an innovative generic class of bioactive agents.

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Authors and Affiliations

  1. Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton, WV1 1LY, UK

    John Howl & Sarah Jones

  2. Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, M1 5GD, UK

    Sabine Matou-Nasri

  3. School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK

    David C. West

  4. School of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Michelle Farquhar & Jane McKeating

  5. Department of Antimicrobial Peptides, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10, Prague 6, Czech Republic

    Jiřina Slaninová

  6. Department of Molecular Medicine and Surgery, Karolinska Institute, 171 77, Stockholm, Sweden

    Claes-Göran Östenson

  7. Medical Faculty, Institute of Biochemistry, University of Ljubljana, 1105, Ljubljana, Slovenia

    Matjaz Zorko

  8. Department of Neurochemistry, Stockholm University, 10691, Stockholm, Sweden

    Pernilla Östlund & Ülo Langel

  9. Faculty of Medical and Human Sciences, School of Medicine, University of Manchester, Manchester, M13 9PT, UK

    Shant Kumar

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  1. John Howl
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  10. Ülo Langel
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Correspondence to John Howl.

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Howl, J., Matou-Nasri, S., West, D.C. et al. Bioportide: an emergent concept of bioactive cell-penetrating peptides. Cell. Mol. Life Sci. 69, 2951–2966 (2012). https://doi.org/10.1007/s00018-012-0979-4

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  • DOI: https://doi.org/10.1007/s00018-012-0979-4

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