Avtor/Urednik     Howl, John; Matou-Nasri, Sabine; West, David C; Zorko, Matjaž
Naslov     Bioportide: an emergent concept of bioactive cell-penetrating peptides
Tip     članek
Vir     Cell Mol Life Sci
Vol. in št.     Letnik 69, št. 17
Leto izdaje     2012
Obseg     str. 2951-66
Jezik     eng
Abstrakt     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.
Deskriptorji     ASTROCYTOMA
CELL MEMBRANE PERMEABILITY
PEPTIDES
RECEPTORS, CALCITONIN
INSULIN
RATS
NITRIC-OXIDE SYNTHASE
SIGNAL TRANSDUCTION
BIOLOGICAL TRANSPORT, ACTIVE
ENDOTHELIUM, VASCULAR
CELL SURVIVAL
CELL DIVISION
HEPATITIS C
CYCLIC AMP
GUANOSINE TRIPHOSPHATE
TRANSLOCATION (GENETICS)
CELLS, CULTURED