Details

Autor(en) / Beteiligte

• Zeman, Steven M.
• Phillips, Don R.
• Crothers, Donald M.

Titel

Characterization of Covalent Adriamycin-DNA Adducts

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (20), p.11561-11565

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Adriamycin is a popular antineoplastic agent whose ability to form covalent adducts with DNA has been correlated to cellular apoptosis (programmed cell death) in tumor models. We have isolated and purified this adduct formed under oxido-reductive (Fenton) conditions in Tris buffer. We show by homo- and heteronuclear NMR spectroscopy that the covalent Adriamycin-DNA adduct is structurally equivalent to that resulting from direct reaction with formaldehyde. Covalent linkage of the drug to one of the DNA strands confers remarkable stability to the duplex, indicated by a 162-fold reduction in the rate of strand displacement compared with the complex with noncovalently bound drug. Glyceraldehyde also engenders covalent Adriamycin-DNA complexes, providing a possible relevant biological context for in vivo adduct formation.