RT Journal Article
SR Electronic
T1 Joint experimental and theoretical investigation of the comparative DNA binding affinities of intercalating anthracycline derivatives.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 251
OP 256
VO 35
IS 2
A1 Gresh, N
A1 Pullman, B
A1 Arcamone, F
A1 Menozzi, M
A1 Tonani, R
YR 1989
UL http://molpharm.aspetjournals.org/content/35/2/251.abstract
AB The comparative binding affinities for poly(dA-dT) and poly(dG-dC) of novel antitumor anthracyclines are reported. The data concern, besides the parent compound adriamycin (ADM), 4-demethoxy 6-deoxy 6-aminodaunomycin (II), 9-deoxy-ADM (III), 4-demethyl-6-O-methyl-ADM (IV), and 3'-deamino-3'-hydroxy-4'-epi-ADM (IV). Theoretical computations are performed in parallel for their comparative binding affinities to model double-stranded hexanucleotides, d(GCGCGC)2, d(TATATA)2, and d(CGTACG)2, using the SIBFA (sum of interactions between fragments computed ab inito) procedure. The computations reproduce in a very satisfactory manner the most salient features of the experimental comparative binding affinities. These encompass, in particular, a higher affinity for the d(TATATA)2 oligomer of II than that of ADM, despite the absence of the 14-OH substituent in II, a marked reversal of the CG versus TA sequence selectivity of the neutral compound V, favoring the d(CGCGCG)2 oligomer over the d(TATATA)2 one; and the deleterious effect incurred on the binding affinities by the presence of an O-methyl substituent at position 6 of the chromophore.