title: Targeting Beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe.
abstract: Biomolecules containing the RGD peptide sequence are known to bind integrins with high affinity. Studies of hexa-and hepta-peptides labeled with a near-infrared fluorescent probe (cypate) showed that rearranging the glycine in a linear RGD peptide sequence to form the GRD analogue favored the uptake of the GRD compound by alphavbeta3 integrin receptor (ABIR)-positive A549 tumor cells and tissue. The internalization of the GRD compound in A549 cells and tumor uptake in mice were inhibited by ABIR-avid peptides, suggesting its recognition by this receptor. Further studies with functional blocking antibodies and beta3 knockout cells revealed that beta3 integrin mediates the internalization of the cypate-GRD peptide. Molecular modeling studies supported preferential interaction of the probe with the beta3 subunit of integrins relative to the alphav subunit. The results demonstrate that the cypate-GRD peptide targets beta3 integrin, thereby providing a strategy to monitor drug delivery and efficacy, and physiopathologic processes mediated by this protein.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Bloch
authors.forename: Baogang
authors.initials: B
authors.lastname: Xu
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.forename: Kexian
authors.initials: K
authors.lastname: Liang
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Nikiforovich
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D015335:Molecular Probes / Q000737:chemistry*; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D039641:Integrin beta Chains; D015335:Molecular Probes; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid