title: Bioportide: an emergent concept of bioactive cell-penetrating peptides.
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.
authors.affiliation: Research Institute in Healthcare Science, School of Applied Sciences, University of Wolverhampton, Wolverhampton, WV1 1LY, UK. J.Howl@wlv.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Howl
authors.forename: Sabine
authors.initials: S
authors.lastname: Matou-Nasri
authors.forename: David C
authors.initials: DC
authors.lastname: West
authors.forename: Michelle
authors.initials: M
authors.lastname: Farquhar
authors.forename: Jiřina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Ostenson
authors.forename: Matjaz
authors.initials: M
authors.lastname: Zorko
authors.forename: Pernilla
authors.initials: P
authors.lastname: Ostlund
authors.forename: Shant
authors.initials: S
authors.lastname: Kumar
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Jane
authors.initials: J
authors.lastname: McKeating
authors.forename: Sarah
authors.initials: S
authors.lastname: Jones
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects*; D057846:Cell-Penetrating Peptides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis; D049033:Chorioallantoic Membrane; D000242:Cyclic AMP / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D021381:Protein Transport; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D057846:Cell-Penetrating Peptides; D007328:Insulin; D000242:Cyclic AMP