A novel peptide, PLAEIDGIELTY, for the targeting of alpha9beta1-integrins

FEBS Letters
H SchneiderC Coutelle

Abstract

Targeting gene therapy vectors to abundant receptors on airway epithelia may allow a significant enhancement of gene delivery and thereby be of particular importance for the gene therapy of cystic fibrosis. Alpha9beta1-integrins are highly expressed throughout the human airway epithelia in vivo, irrespective of any particular clinical status. Aiming to improve the targeting of our non-viral integrin-mediated gene transfer systems to airway epithelia, we searched for a short tenascin C-derived peptide which would bind to these integrins. By utilizing recombinant bacteriophages that display overlapping regions of the third fibronectin type III repeat of tenascin C (TNfn3), we were able to localize its alpha9beta1-integrin binding site to the B-C loop of TNfn3. A synthetic Pro-Leu-Ala-Glu-Ile-Asp-Gly-Ile-Glu-Leu-Thr-Tyr peptide (PLAEIDGIELTY) was shown to displace alpha9beta1-integrin-expressing cells completely from binding to TNfn3. This peptide, therefore, may prove useful both for the examination of the functional importance of alpha9beta1-integrins in vivo and the development of gene therapy vectors or drugs targeting these integrins.

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Citations

Nov 10, 2000·Advanced Drug Delivery Reviews·R J Parkes, S L Hart
Dec 6, 2001·Advanced Drug Delivery Reviews·C PichonP Midoux
Jan 25, 2002·Medicine·Danuta Balicki, Ernest Beutler
Apr 6, 2007·The AAPS Journal·Molly E Martin, Kevin G Rice
Dec 23, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wing-Fu Lai, Marie Chia-Mi Lin
Jun 7, 2005·Chembiochem : a European Journal of Chemical Biology·Jodie E WaterhouseAndrew D Miller
Feb 13, 2001·FEBS Letters·P J JostH Schneider
Oct 13, 2000·Breast Cancer : the Journal of the Japanese Breast Cancer Society·K ArihiroY Yokosaki
Aug 24, 2010·Matrix Biology : Journal of the International Society for Matrix Biology·Helge WiigRaghu Kalluri

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