VISUALIZATION OF DRUG-NUCLEIC ACID INTERACTIONS AT ATOMIC RESOLUTION .9. STRUCTURES OF 2 N,N-DIMETHYLPROFLAVINE - 5-IODOCYTIDYLYL (3'-5') GUANOSINE CRYSTALLINE COMPLEXES
VISUALIZATION OF DRUG-NUCLEIC ACID INTERACTIONS AT ATOMIC RESOLUTION .9. STRUCTURES OF 2 N,N-DIMETHYLPROFLAVINE - 5-IODOCYTIDYLYL (3'-5') GUANOSINE CRYSTALLINE COMPLEXES
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DOI：
10.1080/07391102.1984.10507512
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发表时间：
1984-01-01
影响因子：
4.4
通讯作者：
GABBAY, EJ
中科院分区：
文献类型：
--
作者：
BHANDARY, KK;SAKORE, TD;GABBAY, EJ
Two complexes containing N,N-dimethylproflavine and the dinucleoside monophosphate, 5-iodocytidylyl(3''-5)guanosine (iodoCpG), are described. The first complex is triclinic, space group P1, with unit cell dimensions a = 11.78 .ANG., b = 14.55 .ANG., c = 15.50 .ANG., .alpha. = 89.2.degree., .beta. = 86.2.degree., .gamma. = 96.4.degree.. The second complex is monoclinic, space group P21, with a = 14.20 .ANG., b = 19.00 .ANG., c = 20.73 .ANG., .beta. = 103.6.degree.. Both structures were solved to atomic resolution and refined by Fourier and least squares methods. The 1st structure was refined anisotropically to a residual of 0.09 on 5025 observed reflections using block diagonal least squares, while the 2nd structure was refined isotropically to a residual of 0.13 on 2888 reflections with full matrix least squares. The asymmetric unit in both structures contains 2 dimethylproflavine molecules and 2 iodoCpG molecules; the 1st structure has 16 H2O molecules (a total of 134 non-H atoms), while the 2nd structure has 18 H2O molecules (a total of 136 non-H atoms). Both structures demonstrate intercalation of dimethylproflavine between base-paired iodoCpG dimers. Dimethylproflavine molecules stack on either side of the intercalated duplex, being related by a unit cell translation along b and a axes, respectively. The basic structural feature of the sugar-phosphate chains accompanying dimethylproflavine intercalation in both structures is the mixed sugar puckering pattern: C3'' endo (3''-5'') C2'' endo. This same structural information is demonstrated in another study, which describes a complex containing dimethylproflavine with deoxyribo-CpG. Similar information has already appeared for other simple intercalators such as ethidium, acridine orange, ellipticine, 9-aminoacridine, N-methyl-tetramethylphenanthrolinium and terpyridine platinum. Complex intercalators such as proflavine and daunomycin have given different structural information in model studies. Proflavine and acridine orange are frameshift mutagens that bind to DNA by intercalation. Both compounds form crystalline complexes with a variety of dinucleoside monophosphates, and this has allowed direct visualization of the structural chemistry accompanying intercalation in these model systems.
