Pepducine

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Pepducins are synthetic lipopeptides that activate or inhibit G proteins .

properties

Pepducins consist of short peptides that are derived from G-protein interaction partners and, due to palmitoylation, bind to cell membranes as lipid anchors and, after penetration of the cell membrane, bind to G-proteins, modulating their activity and thus changing signal transduction .

Over 15 pepducins have been described, including GPCR (including PAR1 , PAR2 and PAR4), chemokine receptors ( CXCR1 , CXCR2 and CXCR4 ), sphingosine-1-phosphate receptor 3 (S1P3), melanocortin-4 receptor , smoothened receptor , formyl peptide receptor 2 (FPR2), relaxin receptor (LGR7), G proteins (Gα (q / 11 / o / 13)), muscarinic acetylcholine receptor , TRPV1 ion channels, GPIIb integrin , and the adrenoceptor ADRA1B .

Applications

A CXCR4-binding pepducin is used for indirect molecular labeling . A PAR4 pepducin is being investigated to prevent thrombosis .

history

Pepducine was first described by Lidija Covic and colleagues in 2002. The i3 loop of protease-activated receptors-1 and -2 as well as of the melanocortin-4 receptor was synthesized in N -terminal palmitoylated form .

literature

  • R. Carr, JL Benovic: From biased signaling to polypharmacology: unlocking unique intracellular signaling using pepducins. In: Biochemical Society transactions. Volume 44, Number 2, April 2016, pp. 555-561, doi : 10.1042 / BST20150230 , PMID 27068969 .
  • P. Zhang, L. Covic, A. Kuliopulos: Pepducins and Other Lipidated Peptides as Mechanistic Probes and Therapeutics. In: Methods in molecular biology. Volume 1324, 2015, pp. 191-203, doi : 10.1007 / 978-1-4939-2806-4_13 , PMID 26202271 , PMC 4838413 (free full text).

Individual evidence

  1. ^ S. Kubo, T. Ishiki, I. Doe, F. Sekiguchi, H. Nishikawa, K. Kawai, H. Matsui, A. Kawabata: Distinct activity of peptide mimetic intracellular ligands (pepducins) for proteinase-activated receptor-1 in multiple cells / tissues. In: Annals of the New York Academy of Sciences. Volume 1091, December 2006, pp. 445-459, doi : 10.1196 / annals.1378.087 , PMID 17341635 .
  2. ↑ K. O'Callaghan, A. Kuliopulos, L. Covic: Turning receptors on and off with intracellular pepducins: new insights into G-protein-coupled receptor drug development. In: The Journal of biological chemistry. Volume 287, Number 16, April 2012, pp. 12787-12796, doi : 10.1074 / jbc.R112.355461 , PMID 22374997 , PMC 3339939 (free full text).
  3. ↑ SL Tressel, G. Koukos, B. Tchernychev, SL Jacques, L. Covic, A. Kuliopulos: Pharmacology, biodistribution, and efficacy of GPCR-based pepducins in disease models. In: Methods in molecular biology. Volume 683, 2011, pp. 259-275, doi : 10.1007 / 978-1-60761-919-2_19 , PMID 21053136 , PMC 3780409 (free full text).
  4. ↑ J. Kuil, T. Buckle, FW van Leeuwen: Imaging agents for the chemokine receptor 4 (CXCR4). In: Chemical Society reviews. Volume 41, Number 15, August 2012, pp. 5239-5261, doi : 10.1039 / c2cs35085h , PMID 22743644 .
  5. ↑ A. Kuliopulos, L. Covic: Blocking receptors on the inside: pepducin-based intervention of PAR signaling and thrombosis. In: Life sciences. Volume 74, Number 2-3, December 2003, pp. 255-262, PMID 14607253 .
  6. ↑ L. Covic, AL Gresser, J. Talavera, S. Swift, A. Kuliopulos: Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides. In: Proceedings of the National Academy of Sciences . Volume 99, number 2, January 2002, pp. 643-648, doi : 10.1073 / pnas.022460899 , PMID 11805322 , PMC 117359 (free full text).