Structural comparison of anticancer drug-DNA complexes: Adriamycin and daunomycin

Journal Article · Tue Mar 13 00:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00462a016· OSTI ID:6073960

Frederick, C A; Williams, L D; Rich, A; Wang, A H.J. ^[1]; Ughetto, G ^[2]; van der Marel, G A; van Boom, J H ^[3]

---

1. Massachusetts Institute of Technology, Cambridge (USA)
2. Instituto di Strutturistica Chimica, Rome (Italy)
3. Leiden State Univ. (Netherlands)

The anticancer drugs adriamycin and daunomycin have each been crystallized with the DNA sequence d(CGATCG) and the tree-dimensional structures of the complexes solved at 1.7- and 1.5-{angstrom} resolution, respectively. These antitumor drugs have significantly different clinical properties, yet they differ chemically by only the additional hydroxyl at C14 of adriamycin. The complex of daunoymcin with d(CGATCG) has tighter binding than the complex with d(CGTACG), leading us to infer a sequence preference in the binding of this anthracycline drug. The structures of daunomycin and adriamycin with d(CGATCG) are very similar. However, there add additional solvent interactions with the adriamycin C14 hydroxyl linking it to the DNA. Surprisingly, under the influence of the altered solvation, there is considerable difference in the conformation of spermine in these two complexes. The observed changes in the overall structures of the ternary complexes amplify the small chemical differences between these two antibiotics and provide a possible explanation for the significantly different clinical activities of these important drugs.

• OSTI ID: 6073960
• Journal Information: Biochemistry; (USA), Vol. 29:10; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIBIOTICS
CROSS-LINKING
DNA
DNA ADDUCTS
STEREOCHEMISTRY
ANTINEOPLASTIC DRUGS
CHEMICAL BONDS
CHEMICAL PROPERTIES
DNA REPLICATION
DOXORUBICIN
MOLECULAR STRUCTURE
ADDUCTS
ANTI-INFECTIVE AGENTS
CHEMICAL REACTIONS
DRUGS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POLYMERIZATION
550201* - Biochemistry- Tracer Techniques