<br/>Cis-diamminedichloridoplatinum(II) (cisPt) is a metal-based anticancer drug that is highly potent and widely used for treating different types of solid cancers such as testicular, bladder, lung, cervical, and head, and neck. The N7 positions of purine bases are the most prominent sites of reaction with cisPt, leading to DNA lesions that disrupt cellular functions such as replication and transcription. The lesions created by cisPt cause DNA bending towards the major groove, local unwinding of the duplex, and alteration of the DNA conformation. CisPt also reacts with RNAs and proteins in normal cells, which leads to severe side effects such as nephrotoxicity, ototoxicity, and nausea. In search of compounds with better efficiency and fewer side effects, we have explored a series of cisPt analogs that includes amino acid-linked platinum (II) (AAPt) complexes. We synthesized AAPt compounds with cationic residues to favor interactions with the anionic oligonucleotides. The L and D versions of arginine platin (argPt) and ornithine platin (ornPt) were generated. Previous studies have shown a 34° bend angle towards the major groove of short DNAs following coordination to cisPt. In this study, we determined the bend angles of 22-residue oligonucleotides containing site-specific adducts of the AAPt complexes. To calculate the bend angles of 22-nucleotide DNAs or RNAs induced by AAPt, gel electrophoretic mobility shifts were employed. Our results indicate that the DNA lesions caused by AAPt complexes lead to bending in a manner similar to the parent compound cisPt. The biological implications of these different Pt adducts and induced bend angles will be discussed.

Structural impacts of amino acid-linked platinum complexes on oligonucleotides

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.