A peptoid "antibody surrogate" that antagonizes VEGF receptor 2 activity.
We report a two-color, cell-based screen to identify specific receptor-binding compounds in a combinatorial library of peptoids displayed on beads. We apply this strategy to the isolation of vascular endothelial growth factor receptor 2 (VEGFR2)-binding peptoids. A dimeric derivative of one of these lead compounds is shown to be an antagonist of VEGFR2 activity both in vitro and in vivo. This methodology provides a potentially general route to synthetic molecules that bind integral membrane receptors with affinities and specificities similar to those of antibodies, but which are far smaller and easier to make and manipulate.
Udugamasooriya
D Gomika
DG
Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9185, USA.
Dineen
Sean P
SP
Brekken
Rolf A
RA
Kodadek
Thomas
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D034444:Peptoids / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D008024:Ligands; D034444:Peptoids; D040301:Vascular Endothelial Growth Factor Receptor-2