A theoretical investigation on the sequence selective binding of adriamycin to double-stranded polynucleotides

Abstract

Theoretical computations are performed on the structural and energetical factors Involved In the sequence selective binding of adrlamycln (ADM) to five self-complementary double-stranded hexanucleotldes. Among the two regularly alternating hexanucleotldes d (TATATA)2 and d (CGCGCG)2, a stronger binding Is predicted for the former. The strongest complex is computed, however, for the mixed hexanucleotlde d (CGTACG)2, containing the Intercalation site between two CO base pairs and an adjacent TA base pair. The overall sequence preference is the resut of an intricate interplay of sequence preferences of the constituents In particular of daunosamlne and the 9-OH aubstltuent. Altogether, the selective base pair recognition by adrlamycln cannot be defined in terms of the two base pairs implicated in the intercalation site alone but must be expressed In terms of a triplet of base pairs. © 1986 IRL Press Limited.