Bioportide: an emergent concept of bioactive cell-penetrating peptides

John Howl, Sabine Matou-Nasri, David C West, Michelle Farquhar, Jiřina Slaninová, Claes-Göran Ostenson, Matjaz Zorko, Pernilla Ostlund, Shant Kumar, Ulo Langel, Jane McKeating, Sarah Jones

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2951-66
Number of pages16
JournalCellular and Molecular Life Sciences
Volume69
Issue number17
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Animals
  • Aorta
  • Astrocytoma
  • Brain
  • Cattle
  • Cell Membrane Permeability
  • Cell-Penetrating Peptides
  • Cells, Cultured
  • Chemotaxis
  • Chorioallantoic Membrane
  • Cyclic AMP
  • Dermis
  • Diabetes Mellitus, Type 2
  • Drug Delivery Systems
  • Endocytosis
  • Endothelium, Vascular
  • Female
  • Hepacivirus
  • Hepatitis C
  • Humans
  • Insulin
  • Islets of Langerhans
  • Male
  • Neovascularization, Physiologic
  • Protein Transport
  • Quantitative Structure-Activity Relationship
  • Rats
  • Rats, Wistar
  • Urinary Bladder Neoplasms
  • Uterine Contraction

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