RT Journal Article
SR Electronic
T1 Synthesis and characterization of a high-affinity α<sub>v</sub>β<sub>6</sub>-specific ligand for <em>in vitro</em> and <em>in vivo</em> applications
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 1239
OP 1249
DO 10.1158/1535-7163.MCT-08-1098
VO 8
IS 5
A1 Li, Shunzi
A1 McGuire, Michael J.
A1 Lin, Mai
A1 Liu, Ying-Horng
A1 Oyama, Tsukasa
A1 Sun, Xiankai
A1 Brown, Kathlynn C.
YR 2009
UL http://mct.aacrjournals.org/content/8/5/1239.abstract
AB The αvβ6 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 αvβ6. 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 αvβ6 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 αvβ6 will find clinical use as a diagnostic and therapeutic reagent. [Mol Cancer Ther 2009;8(5):1239–49]