Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequence specificity of DNA-binding by monoaza- and diaza-anthracenedione analogues of mitoxantrone (MX) has been investigated by DNase 1 footprinting and spectroscopic techniques. More than 100 sites cut by the enzyme were sequenced on three pBR 322 and simian virus 40 DNA restriction fragments. Different inhibition and stimulation effects were observed as a function of the structural properties of each drug. A gradual change was found from MX to monoaza derivatives and from these to diaza derivatives, corresponding to a broader distribution of drug-inhibited regions. In addition to almost all sites found with MX (38 of 44), 29 new inhibition sites were observed using the diaza compound BBR 2894. The sequence analyses in terms of base doublets or triplets confirm the preference of MX for alternating pyrimidine-purine sites, the most significant triplet sequences being (5' to 3') CTA, GCA, TAC, ACT, CAC and TTA. In addition to MX sites, BBR 2894 seemed to bind efficiently to pyrimidine-pyrimidine-pyrimidine or purine-pyrimidine-pyrimidine triplets containing CT or TC motifs. Differential cleavage plots essentially confirmed the above results. Spectrophotometric and chiroptical studies showed a decreased DNA-binding affinity and a modified geometry of intercalation when nitrogen replaces carbon in the anthraquinone ring. These results can be useful for understanding the substantially different biological responses exhibited by aza-substituted anthracenedlones when compared with their non-substituted, pharmacologically relevant congeners.
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PMID:Aza-bioisosteres of 9, 10-anthracenedione: a modulation of DNA sequence specificity. 886 28