X-Ray analysis of 2',3'-lyxoanhydrothymidine, a conformationally restricted inhibitor of retroviral reverse transcriptases

• Published in: FEBS letters Vol. 265; no. 1; pp. 63 - 66
• Main Authors: Gurskaya, Galyna V., Bochkarev, Alexey V., Zdanov, Alexander S., Papchikhin, Alexander V., Purygin, Piotr P., Krayevsky, Alexander A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.06.1990; Elsevier
• Subjects: 2',3'-Lyxoanhydrothymidine; Analytical, structural and metabolic biochemistry; Antiviral Agents; Biological and medical sciences; DNA biosynthesis; Fundamental and applied biological sciences. Psychology; Models, Molecular; Molecular Conformation; Nucleic acids; Nucleic bases, nucleotides; Retroviridae - enzymology; Reverse transcriptase; Reverse Transcriptase Inhibitors; Thymidine - analogs & derivatives; Thymidine - pharmacology; X-ray analysis; X-Ray Diffraction; DNA biosynthesis; 2',3'-Lyxoanhydrothymidine; X-ray analysis; Reverse transcriptase; Virus; Structure activity relation; Thymine derivatives; DNA polymerase RNA-dependent; Enzyme inhibitor; Nucleotide; Retroviridae; X ray diffraction; Conformation; Crystalline structure
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)80884-L

2',3'-Lyxoanhydrothymidine (LAT), a conformationally restricted inhibitor of retroviral reverse transcriptases, has been studied by X-ray analysis. The unit cell contains two crystallographically independent molecules A and B. Their sugar moieties have an identical structure: an 04'- endo pucker of the furanose cycle and a trans conformation about the exocyclic C4'-C5' bond. The conformations of A and B molecules differ with respect to the N-glycosidic bond: χA(04 ‘Cl’ N1C2) = −121.9° which is typical of a common anti conformation whereas χB (04‘Cl’N1C2) = 121.2° corresponds to a rare high- syn conformation. All the conformation properties of LAT molecules stem from the presence of an epoxide cycle in their molecules.