Synthesis and characterization of a high-affinity α vβ 6-specific ligand for in vitro and in vivo applications

Shunzi Li, Michael J. McGuire, Mai Lin, Ying Horng Liu, Tsukasa Oyama, Xiankai Sun, Kathlynn C. Brown

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The α vβ 6 integrin is an attractive therapeutic target for several cancers due to its role in metastasis and its negligible expression in normal tissues. We previously identified a peptide from a phage-displayed peptide library that binds specifically to α vβ 6. The tetrameric version of the peptide has higher affinity for its cellular targets than the corresponding monomers. However, the inefficient synthesis limits its clinical potential. We report here a convergent synthesis producing the tetrameric peptide in high yield and purity. The ease of the synthesis allows for rapid optimization of the peptide. We have optimized this α vβ 6 integrin-binding peptide, determining the minimal binding domain and valency. Importantly, the half-maximal binding affinity of the optimal peptide for its target cell is in the 40 to 60 pmol/L range, rivaling the affinity of commonly used antibody-targeting reagents. This peptide mediates cell-specific uptake, is functional in diagnostic formats, is stable in sera, and can home to a tumor in an animal. We anticipate that this high-affinity ligand for α vβ 6 will find clinical use as a diagnostic and therapeutic reagent.

Original languageEnglish (US)
Pages (from-to)1239-1249
Number of pages11
JournalMolecular Cancer Therapeutics
Volume8
Issue number5
DOIs
StatePublished - May 1 2009

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Ligands
Peptides
Integrins
Peptide Library
In Vitro Techniques
Bacteriophages
Neoplasms
Neoplasm Metastasis
Antibodies
Therapeutics
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Synthesis and characterization of a high-affinity α vβ 6-specific ligand for in vitro and in vivo applications. / Li, Shunzi; McGuire, Michael J.; Lin, Mai; Liu, Ying Horng; Oyama, Tsukasa; Sun, Xiankai; Brown, Kathlynn C.

In: Molecular Cancer Therapeutics, Vol. 8, No. 5, 01.05.2009, p. 1239-1249.

Research output: Contribution to journalArticle

Li, Shunzi ; McGuire, Michael J. ; Lin, Mai ; Liu, Ying Horng ; Oyama, Tsukasa ; Sun, Xiankai ; Brown, Kathlynn C. / Synthesis and characterization of a high-affinity α vβ 6-specific ligand for in vitro and in vivo applications. In: Molecular Cancer Therapeutics. 2009 ; Vol. 8, No. 5. pp. 1239-1249.
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