N-Methylmesoporphyrin IX Exhibits G-Quadruplex-Specific Photocleavage Activity

Dominic McBrayer; Michelle Schoonover; Kimberly J Long; Ruby Escobedo; Sean M Kerwin

doi:10.1002/cbic.201900002

N-Methylmesoporphyrin IX Exhibits G-Quadruplex-Specific Photocleavage Activity

Chembiochem. 2019 Aug 1;20(15):1924-1927. doi: 10.1002/cbic.201900002. Epub 2019 May 27.

Authors

Dominic McBrayer¹, Michelle Schoonover¹, Kimberly J Long², Ruby Escobedo², Sean M Kerwin²

Affiliations

¹ Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas, 107 W. Dean Keaton, Austin, TX, 78712, USA.
² Department of Chemistry and Biochemistry, Texas State University, 601 University Drive, San Marcos, TX, 78666, USA.

PMID: 30850998
DOI: 10.1002/cbic.201900002

Abstract

N-Methylmesoporphyrin IX (NMM) has long been known as a G-quadruplex DNA (G4) ligand. However, there has been little investigation into its G-quadruplex photocleavage activity. Herein, we demonstrate that NMM is a highly selective photocleavage agent for G4 structures but not duplex DNA. Analysis of the cleavage products by PAGE demonstrates that G4 photocleavage by NMM occurs at sites similar to those cleaved by TMPyP4, a nonselective DNA photocleavage agent. Although NMM is shown here to generate singlet oxygen in the presence of both duplex and G4, the lack of increased photocleavage in D₂ O indicated that singlet oxygen is not involved in the photocleavage of G4 by NMM.

Keywords: G-quadruplexes; photocleavage; porphyrins; singlet oxygen.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

DNA / chemistry*
G-Quadruplexes
Mesoporphyrins / chemistry*
Molecular Structure
Photochemical Processes

Substances

Mesoporphyrins
N-methylmesoporphyrin IX
DNA