PMID- 9875412
OWN - NLM
STAT- MEDLINE
DCOM- 19990210
LR  - 20201209
IS  - 0956-3202 (Print)
IS  - 0956-3202 (Linking)
VI  - 9
IP  - 4
DP  - 1998 Jul
TI  - Novel 3'-spiro nucleoside analogues of TSAO-T. Part II. A comparative study based 
      on NMR conformational analysis in solution and theoretical calculations.
PG  - 333-40
AB  - The structures of two novel 3'-spiro nucleosides analogues of the potent human 
      immunodeficiency virus type 1 (HIV-1) reverse trancriptase (RT) inhibitor 
      TSAO-m3T, in solution, as derived from NMR spectroscopy are described. In these 
      TSAO analogues the spiro amino oxathioledioxide moiety has been replaced by spiro 
      amino oxazolone or spiro amino oxathiazoledioxide moieties. A comparative study 
      based on theoretical calculations of the hydrophobicity, the solvation free 
      energies and molecular electrostatic potentials (MEP) of the three compounds is 
      also described. No significant conformational differences were detected in 
      solution between TSAO-m3T and its analogues that might account for the 
      differences observed in their inhibitory activity against HIV-1 RT. The 
      calculated hydrophobicity (log P) values, dipole moments and the electrostatic 
      contributions to the solvation free energies of the three spiro ring systems were 
      also similar. However, the differences found in the calculated MEPs of the spiro 
      systems between TSAO-m3T and its analogues suggest that the different 
      electrostatic surroundings of the 4"-amino group of the spiro moiety in the 
      analogues may be responsible for a detrimental electrostatic interaction of the 
      spiro rings with the Glu-B138 of RT.
FAU - Alvarez, R
AU  - Alvarez R
AD  - Instituto de Quimica Medica (CSIC), Madrid, Spain.
FAU - Jimeno, M L
AU  - Jimeno ML
FAU - Gago, F
AU  - Gago F
FAU - Balzarini, J
AU  - Balzarini J
FAU - Perez-Perez, M J
AU  - Perez-Perez MJ
FAU - Camarasa, M J
AU  - Camarasa MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Chem Chemother
JT  - Antiviral chemistry & chemotherapy
JID - 9009212
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Nucleosides)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (Spiro Compounds)
RN  - 142102-79-2 
      (1-(2',5'-bis-O-(tert-butyldimethylsilylribofuranosyl)-3-N-methylthymine)-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide))
RN  - VC2W18DGKR (Thymidine)
RN  - WF66Y930KH (TSAO-T)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Anti-HIV Agents/chemistry
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Molecular Structure
MH  - Nucleosides/*chemistry
MH  - Reverse Transcriptase Inhibitors/*chemistry
MH  - Spiro Compounds/*chemistry
MH  - Static Electricity
MH  - Thymidine/*analogs & derivatives/chemistry
MH  - Uridine/analogs & derivatives
EDAT- 1999/01/06 00:00
MHDA- 1999/01/06 00:01
CRDT- 1999/01/06 00:00
PHST- 1999/01/06 00:00 [pubmed]
PHST- 1999/01/06 00:01 [medline]
PHST- 1999/01/06 00:00 [entrez]
PST - ppublish
SO  - Antivir Chem Chemother. 1998 Jul;9(4):333-40.