A novel peptide, PLAEIDGIELTY, for the targeting of alpha9beta1-integrins.
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.
Schneider
H
H
Section of Molecular Genetics, Division of Biomedical Sciences, Imperial College School of Medicine at St Mary's Hospital, London, UK. h.schneider@ic.ac.uk
Harbottle
R P
RP
Yokosaki
Y
Y
Kunde
J
J
Sheppard
D
D
Coutelle
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D017912:Inovirus / Q000235:genetics; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*
D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D019063:Tenascin; C113256:integrin alpha 9 beta 1