Targeting beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe

Sharon Bloch, Baogang Xu, Yunpeng Ye, Kexian Liang, Gregory V. Nikiforovich, Samuel Achilefu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 αvβ3 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 β3 knockout cells revealed that β3 integrin mediates the internalization of the cypate-GRD peptide. Molecular modeling studies supported preferential interaction of the probe with the β3 subunit of integrins relative to the αv subunit. The results demonstrate that the cypate-GRD peptide targets β3 integrin, thereby providing a strategy to monitor drug delivery and efficacy, and physiopathologic processes mediated by this protein.

Original languageEnglish (US)
Pages (from-to)539-549
Number of pages11
JournalMolecular Pharmaceutics
Volume3
Issue number5
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Cancer
  • Imaging
  • Integrin
  • Molecular probe
  • Near-infrared

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Targeting beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe'. Together they form a unique fingerprint.

Cite this