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Cellular and Molecular Life Sciences

, Volume 69, Issue 17, pp 2951–2966 | Cite as

Bioportide: an emergent concept of bioactive cell-penetrating peptides

  • John Howl
  • Sabine Matou-Nasri
  • David C. West
  • Michelle Farquhar
  • Jiřina Slaninová
  • Claes-Göran Östenson
  • Matjaz Zorko
  • Pernilla Östlund
  • Shant Kumar
  • Ülo Langel
  • Jane McKeating
  • Sarah Jones
Research Article

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.

Keywords

Angiogenesis Bioportide Camptide Cell-penetrating peptide Nosangiotide Second messenger Insulin secretion Viral infectivity 

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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • John Howl
    • 1
  • Sabine Matou-Nasri
    • 2
  • David C. West
    • 3
  • Michelle Farquhar
    • 4
  • Jiřina Slaninová
    • 5
  • Claes-Göran Östenson
    • 6
  • Matjaz Zorko
    • 7
  • Pernilla Östlund
    • 8
  • Shant Kumar
    • 9
  • Ülo Langel
    • 8
  • Jane McKeating
    • 4
  • Sarah Jones
    • 1
  1. 1.Research Institute in Healthcare Science, School of Applied SciencesUniversity of WolverhamptonWolverhamptonUK
  2. 2.Institute for Biomedical Research into Human Movement and HealthManchester Metropolitan UniversityManchesterUK
  3. 3.School of Biological SciencesUniversity of LiverpoolLiverpoolUK
  4. 4.School of Immunity and InfectionUniversity of BirminghamBirminghamUK
  5. 5.Department of Antimicrobial PeptidesInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech RepublicPrague 6Czech Republic
  6. 6.Department of Molecular Medicine and SurgeryKarolinska InstituteStockholmSweden
  7. 7.Medical Faculty, Institute of BiochemistryUniversity of LjubljanaLjubljanaSlovenia
  8. 8.Department of NeurochemistryStockholm UniversityStockholmSweden
  9. 9.Faculty of Medical and Human SciencesSchool of Medicine, University of ManchesterManchesterUK

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