Identification of a murine ICAM-1-specific peptide by subtractive phage library selection on cells.
The ICAM-1 adhesion molecule is expressed selectively at low levels on endothelial cells but is strongly upregulated in dysfunctional endothelial cells associated with inflammation, cancer, and atherogenesis. Using COS-7 cells transfected with murine ICAM-1 (mICAM-1) as a target receptor, a phage display library was screened. Clones were selected by elution with a mAb specific for a functional epitope of ICAM-1 and a novel peptide sequence binding to the extracellular domain of mICAM-1 was identified that can potentially be used as a targeting vector aimed at dysfunctional endothelium. We further showed that the targeting specificity of the peptide was retained following its incorporation at the N terminal end of a large chimeric protein. Moreover, this chimeric protein containing the mICAM-1-specific sequence was found to inhibit ICAM-1-mediated intercellular adhesion during antigen presentation. Taken together, these results demonstrate the potential for improving the cell-selectivity and properties of therapeutical agents toward targeting adhesion molecules involved in cell-cell interactions.
Bélizaire
Anna-Karine
AK
Supratek Pharma Inc. Laval, QC, Canada.
Tchistiakova
Lioudmila
L
St-Pierre
Yves
Y
Alakhov
Valery
V
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001667:Binding, Competitive; D019556:COS Cells; D002460:Cell Line; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology
D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1