Document 0578
 DOCN  M9460578
 TI    Solid-state and solution conformations of the potent HIV inhibitor,
       4'-azidothymidine.
 DT    9404
 AU    Maag H; Nelson JT; Steiner JL; Prisbe EJ; Institute of Bio-Organic
       Chemistry, Syntex Discovery Research,; Palo Alto, California 94304.
 SO    J Med Chem. 1994 Feb 18;37(4):431-8. Unique Identifier : AIDSLINE
       MED/94166043
 AB    The three-dimensional structure of 4'-azidothymidine has been determined
       for the solid state and in solution. X-ray crystal analysis indicates
       the presence of two independent molecules (A and B) having the following
       conformational parameters: Phase angles, PA = 13.7 degrees, PB = 12.6
       degrees (C3'-endo envelope); puckering amplitude psi mA = 32.4 degrees,
       psi mB = 37.2 degrees; glycosyl torsion angle chi A = -88.2 degrees, chi
       B = -71.2 degrees; 4'-5' torsion angle gamma A = 58.5 degrees, gamma B =
       36.0 degrees. The solution conformation was determined from NMR coupling
       constants in D2O. Analysis using the computer programs PSEUROT and DAERM
       yielded phase angles (P) of 53.2 degrees (C4'-exo envelope) (major
       conformer) and 63 degrees (C4'-exo envelope), respectively, with
       corresponding puckering amplitudes (psi m) of 34.9 degrees and 45.8
       degrees. A gated 13C NMR experiment was used to determine the 1H-13C
       vicinal coupling constants used to calculate the solution glycosyl
       torsion angle (chi) to be either -80 degrees or -160 degrees and a 4'-5'
       torsion angle, gamma, of ca. 180 degrees. These studies show that
       4'-azidothymidine is conformationally exceptional among the
       antiretroviral nucleosides both as a solid and in solution. The C3'-endo
       (northern) conformation determined by X-ray crystallography is rare
       among HIV-inhibitory nucleosides which usually exist in the solid state
       in a southern conformation. The solution structure is even more peculiar
       in that it exists in the extremely rare 4'-exo envelope conformation.
 DE    Antiviral Agents/*CHEMISTRY/PHARMACOLOGY  Crystallography, X-Ray
       HIV/DRUG EFFECTS  Molecular Conformation  Nuclear Magnetic Resonance
       Stereoisomers  Virus Inhibitors/CHEMISTRY/PHARMACOLOGY
       Zidovudine/*ANALOGS & DERIVATIVES/CHEMISTRY/PHARMACOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).