In vitro selection of a peptide with high selectivity for cardiomyocytes in vivo

Michael J. McGuire, Kausar N. Samli, Stephen Albert Johnston, Kathlynn C. Brown

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

One approach to targeted therapies for cardiovascular disease relies on isolating ligands that enhance the tissue-specific uptake of genes or drugs by heart cells. To obtain heart-targeting ligands, phage display biopanning was used to isolate a 20-mer peptide that binds to isolated primary cardiomyocytes. The isolated phage, PCM.1, displays the peptide WLSEAGPVVTVRALRGTGSW, and binds these cells 180 times better than a control phage from the library. Furthermore, phage displaying this peptide preferentially bind to cardiomyocytes when compared with a panel of other cell types. A BLAST search revealed that this peptide contains a 12 amino acid segment with sequence identity to a peptide in tenascin-X, an extracellular matrix protein. Synthetic peptides containing the complete 20-mer or a 12-mer tenascin peptide partially blocked phage binding to the cardiomyocytes. We developed a quantitative real-time PCR assay to assess uptake of this phage by tissues in vivo. Using this assay, preferential localization of the PCM.1 phage in heart was observed compared to the uptake of this phage by other tissues or other phage by heart. Furthermore, PCM.1 phage was associated with cardiomyocytes isolated from mice treated with a phage in vivo. These results demonstrate the utility of biopanning on isolated cells for identifying specific binding peptides that can target a tissue in vivo.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalJournal of molecular biology
Volume342
Issue number1
DOIs
StatePublished - Sep 3 2004
Externally publishedYes

Keywords

  • APCM, adherent primary cardiomyocytes
  • PCM, primary cardiomyocytes
  • PCM.1, phage displaying the peptide specific for PCM
  • cardiomyocyte
  • cell targeting
  • peptide library
  • peptides
  • phage display

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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