Cysteine-Directed Bioconjugation of a Platinum(II)-Acridine Anticancer Agent

Xiyuan Yao; Christopher M Tracy; Ulrich Bierbach

doi:10.1021/acs.inorgchem.8b02717

Cysteine-Directed Bioconjugation of a Platinum(II)-Acridine Anticancer Agent

Inorg Chem. 2019 Jan 7;58(1):43-46. doi: 10.1021/acs.inorgchem.8b02717. Epub 2018 Dec 13.

Authors

Xiyuan Yao¹, Christopher M Tracy¹, Ulrich Bierbach¹

Affiliation

¹ Department of Chemistry , Wake Forest University , Wake Downtown Campus , Winston-Salem , North Carolina 27101 , United States.

PMID: 30543413
DOI: 10.1021/acs.inorgchem.8b02717

Abstract

Classical maleimide Michael addition chemistry in conjunction with copper-free click chemistry was investigated as a synthetic strategy to attach cytotoxic platinum-acridine hybrid agents to carrier proteins. The structural integrity and selectivity of the model payloads, which were validated in human serum albumin (HSA) using mass spectrometric analysis and heteronuclear 2D ¹H-¹⁵N HSQC NMR experiments, may have broad utility for the targeted delivery of highly cytotoxic platinum acridines and other nonclassical platinum containing anticancer agents.

MeSH terms

Acridines / chemical synthesis
Acridines / chemistry
Acridines / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Click Chemistry
Cysteine / chemistry*
Drug Carriers / chemistry*
Humans
Organoplatinum Compounds / chemical synthesis
Organoplatinum Compounds / chemistry
Organoplatinum Compounds / pharmacology*
Proof of Concept Study
Recombinant Proteins / chemistry
Serum Albumin, Human / chemistry*

Substances

Acridines
Antineoplastic Agents
Drug Carriers
Organoplatinum Compounds
Recombinant Proteins
Cysteine
Serum Albumin, Human