A NOVEL PEPTIDE, PLAEIDGIELTY, FOR THE TARGETING OF ALPHA(9)BETA(1)-INTEGRINS

Targeting gene therapy vectors to abundant receptors on airway epithel ia may allow a significant enhancement of gene delivery and thereby be of particular importance for the gene therapy of cystic fibrosis, alp ha(9)beta(1)-Integrins are highly expressed throughout the human airwa y epithelia in vivo, irrespective of any particular clinical status. A iming to improve the targeting of our non-viral integrin-mediated gene transfer systems to airway epithelia, we searched for a short tenasci n C-derived peptide which would bind to these integrins, By utilizing recombinant bacteriophages that display overlapping regions of the thi rd fibronectin type III repeat of tenascin C (TNfn3), we were able to localize its alpha(9)beta(1)-integrin binding site to the B-C loop of TNfn3. A synthetic eu-Ala-Glu-Ile-Asp-Gly-Ile-Glu-Leu-Thr-Tyr-peptide (PLAEIDGIELTY) was shown to displace alpha(9)beta(1)-integrin-expressi ng cells completely from binding to TNfn3. This peptide, therefore, ma y prove useful both for the examination of the functional importance o f alpha(9)beta(1)-integrins in vivo and the development of gene therap y vectors or drugs targeting these integrins. (C) 1998 Federation of E uropean Biochemical Societies.