Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting.

ABSTRACT: RGD-α-amanitin and isoDGR-α-amanitin conjugates were synthesized by joining integrin ligands to α-amanitin via various linkers and spacers. The conjugates were evaluated for their ability to inhibit biotinylated vitronectin binding to the purified α_Vβ₃ receptor, retaining good binding affinity, in the same nanomolar range as the free ligands. The antiproliferative activity of the conjugates was evaluated in three cell lines possessing different levels of α_Vβ₃ integrin expression: human glioblastoma U87 (α_Vβ₃+), human lung carcinoma A549 (α_Vβ₃-) and breast adenocarcinoma MDA-MB-468 (α_Vβ₃-). In the U87, in the MDA-MB-468, and partly in the A549 cancer cell lines, the cyclo[DKP-isoDGR

SUBMITTER: Bodero L 

PROVIDER: S-EPMC5827777 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature