Cell-Penetrating Peptides: Processes and Applications by Ulo Langel

By Ulo Langel

One of many significant issues of drug supply is the lack of huge hydrophilic compounds to go through the lipid membrane of the mobilephone, hence making medicines comparable to polypeptides and oligonucleotides of constrained healing worth. till lately, the delivery of such molecules into the cytoplasmic and nuclear booths of residing cells appeared target. as a result, the invention that peptides derived from the HIV Tat protein and homeodomain of the Antennapedia transcription issue (penetratin) can translocate around the plasma membrane of stay cells has spread out fascinating new probabilities in biomedical research.This publication fills the necessity for a entire replace of the examine pertaining to those really expert peptides, known as cell-penetrating peptides (CPPs), to which the drug molecule can connect and go through the mobile membrane. Divided into 3 elements, Cell-Penetrating Peptides: methods and purposes covers periods of cell-penetrating peptides; mechanisms of mobile penetration, interactions of cell-penetrating peptides with plasma membranes, and lipid types; and purposes of cell-penetrating peptides. those divisions hide all details from easy biochemistry to medical software, together with a transparent description of the final principles for mobile uptake of the shipping peptides. The evaluate of labor during this quarter will result in larger designed novel delivery peptides to accomplish the extra profitable program of CPPs in examine and remedy.

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Highly specific, membrane-permeant peptide blockers of cGMP-dependent protein kinase Ialpha inhibit NO-induced cerebral dilation, Proc. Natl. Acad. Sci. USA, 97, 14772–14777, 2000. 59. Bonny, C. , Cell-permeable peptide inhibitors of JNK: novel blockers of betacell death, Diabetes, 50, 77–82, 2001. 60. Li, H. , Cholesterol binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide, Proc.

Cholesterol binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide, Proc. Natl. Acad. Sci. USA, 98, 1267–1272, 2001. 61. Stein, S. , 458, 383–386, 1999. 62. J. , Intracellular delivery of a Tat-eGFP fusion protein into muscle cells, Mol. , 3, 310–318, 2001. 63. , Getting hydrophilic compounds into cells: lessons from homeopeptides, Curr. Opin. , 6, 629–634, 1996.

23 The huge difference in the nature and size of these Tat-conjugated entities (a bacteriophage vs. a small peptide) could explain these apparent contradictory results; the possible involvement of caveolae in CPP uptake remains to be convincingly established. 14,15,27,28,33,36,39,58-62 Whether a single pathway is involved in all cases has yet to be evaluated. Whether binding to other cell surface determinants (for instance, to polar lipid heads) is required has also to be further investigated. 42 This feature strongly suggests that a direct interaction with unknown cellular entities is requested to trigger the internalization process.

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