Premium
Characterization of the sequential non‐covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy
Author(s) -
Pavlopoulos Spiro,
Bicknell Wendy,
Wickham Geoffrey,
Craik David J.
Publication year - 1999
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/(sici)1099-1352(199911/12)12:6<346::aid-jmr476>3.0.co;2-l
Subject(s) - chromophore , intercalation (chemistry) , chemistry , covalent bond , titration , dna , nuclear magnetic resonance spectroscopy , stereochemistry , sequence (biology) , two dimensional nuclear magnetic resonance spectroscopy , crystallography , photochemistry , organic chemistry , biochemistry
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 bisepoxide‐containing 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. Copyright © 1999 John Wiley & Sons, Ltd.