Characterization of the sequential non-covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy

✍ Scribed by Spiro Pavlopoulos; Wendy Bicknell; Geoffrey Wickham; David J. Craik

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 140 KB
• Volume: 12
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/(sici)1099-1352(199911/12)12:6<346::aid-jmr476>3.0.co;2-l

✦ Synopsis

Hedamycin, a member of the pluramycin class of antitumour antibiotics, consists of a planar anthrapyrantrione chromophore to which is attached two aminosugar rings at one end and a bisepoxidecontaining sidechain at the other end. Binding to double-stranded DNA is known to involve both reversible and non-reversible modes of interaction. As a part of studies directed towards elucidating the structural basis for the observed 5'-pyGT-3' sequence selectivity of hedamycin, we conducted one-dimensional NMR titration experiments at low temperature using the hexadeoxyribonucleotide duplexes d(CACGTG) 2 and d(CGTACG) 2 . Spectral changes which occurred during these titrations are consistent with hedamycin initially forming a reversible complex in slow exchange on the NMR timescale and binding through intercalation of the chromophore. Monitoring of this reversible complex over a period of hours revealed a second type of spectral change which corresponds with formation of a non-reversible complex.