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Cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-AsP-containing peptide

Item Type:Article
Title:Cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-AsP-containing peptide
Creators Name:Hart, S.L. and Knight, A.M. and Harbottle, R.P. and Mistry, A. and Hunger, H.D. and Cutler, D.F. and Williamson, R. and Coutelle, C.
Abstract:Ligands that bind mammalian cell surface integrins with high affinity can mediate cellular internalization. We show that particles of the bacteriophage fd that display the cyclic integrin-binding peptide sequence GGCRGDMFGC in a proportion of their major coat protein subunits bind to cells and are efficiently internalized. In the displayed peptide the conformation of the RGD motif is restricted within a hairpin loop formed by a disulfide bridge between the 2 cysteine residues. Cellular internalization of phage was demonstrated by confocal and non-confocal immunofluorescence microscopy of tissue-cultured cells incubated with phage particles. The phage were contained in juxtanuclear vesicles in the same serial sections as transferrin receptor but were not colocalized with the cell surface marker alkaline phosphatase. Cell binding and internalization was inhibited by preincubation of cells with the integrin-binding peptide GRGDSP, whereas the control peptide GRGESP had no inhibitory effect. These results indicate that cyclic integrin-binding peptides can be used to target and enter cells and that it should be possible to exploit such peptides for the introduction of DNA, drugs, or other macromolecules.
Keywords:Amino Acid Sequence, Base Sequence, Capsid Proteins, Cell Adhesion, Cell Line, Cyclic Peptides, Fluorescence Microscopy, Inovirus, Integrins, Molecular Sequence Data, Oligodeoxyribonucleotides, Oligopeptides, Recombinant Fusion Proteins
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:12468-12474
Date:29 April 1994
Official Publication:http://www.jbc.org/content/269/17/12468.abstract
PubMed:View item in PubMed

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