Azidothymidine: crystal structure and possible functional role of the azido group.
作者信息
Camerman A, Mastropaolo D, Camerman N
机构信息
Department of Neurology, University of Washington, Seattle 98195.
出版信息
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8239-42. doi: 10.1073/pnas.84.23.8239.
Abstract
The crystal and molecular structures of the anti-acquired immunodeficiency syndrome agent 3'-azido-3'-deoxythymidine (AZT) have been determined by x-ray diffraction. There are two crystallographically independent AZT molecules in the crystal asymmetric unit; they have similar conformations and differ primarily in the glycosyl torsion angle. Comparisons with a hydrated thymidylate structure indicate that the azido group does not significantly affect the gross conformational preference of the molecule. The comparisons also suggest possible functional roles for the azido group in enzyme binding.
摘要
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1
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Science. 1987 Mar 20;235(4795):1462-3. doi: 10.1126/science.3469753.
2
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Biochem Biophys Res Commun. 1987 Jan 15;142(1):128-34. doi: 10.1016/0006-291x(87)90460-8.
3
Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex.
Lancet. 1986 Mar 15;1(8481):575-80. doi: 10.1016/s0140-6736(86)92808-4.
4
Inhibition of reverse transcriptase activity by 2',3'-dideoxythymidine 5'-triphosphate and its derivatives modified on the 3' position.
Biochem Biophys Res Commun. 1986 Oct 30;140(2):498-507. doi: 10.1016/0006-291x(86)90760-6.
5
Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.
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6
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7
Molecular structure of a deoxyribose-dinucleotide, sodium thymidylyl-(5' yields to 3')-thymidylate-(5') hydrate (pTpT), and a possible structural model for polythymidylate.
J Mol Biol. 1976 Nov 15;107(4):601-21. doi: 10.1016/s0022-2836(76)80086-1.
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