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Construction and application of a Rh-Pt DNA metalloinsertor conjugate.

ABSTRACT: We report the synthesis and characterization of a bimetallic conjugate (RhPt) in which an oxaliplatin derivative is tethered to a rhodium metalloinsertor through an aminomalonate leaving group ligand. The complex interacts with DNA through metalloinsertion at a base pair mismatch followed by formation of a covalent Pt-DNA adduct. Characterization of RhPt in mismatch repair-deficient HCT116O cells reveals increased cytotoxicity compared to cisplatin and oxaliplatin as well as relative to the unconjugated rhodium and platinum counterparts. Caspase and poly-ADP ribose polymerase inhibition assays indicate that RhPt induces apoptotic cell death. Inductively coupled plasma mass spectrometry (ICP-MS) experiments reveal that RhPt exhibits enhanced cellular uptake properties that contribute to its increased efficacy.

SUBMITTER: Weidmann AG

PROVIDER: S-EPMC4123934 | biostudies-literature |

REPOSITORIES: biostudies-literature

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DNA strand cleavage near a CC mismatch directed by a metalloinsertor.

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