Conformationally restricted nucleosides. The reaction of adenosine deaminase with substrates built on a bicyclo[3.1.0]hexane template.
Adenosine deaminase (ADA) can discriminate between two distinct (North and South), conformationally rigid substrate conformers. (N)-methanocarba-2'dA (4) is deaminated 100 times faster than the antipodal (S)-methanocarba-2'dA (5), whereas a non-rigid analogue, aristeromycin (6), is deaminated at an intermediate rate. These results are in agreement with crystallographic data from ADA-ribonucleoside complexes showing the furanose ring of the bound purine in a C3'-endo (North) conformation. The data presented here suggests that 4 and 5 are useful probes to ascertain conformational preferences by purine metabolizing enzymes.
Marquez
V E
VE
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Russ
P
P
Alonso
R
R
Siddiqui
M A
MA
Shin
K J
KJ
George
C
C
Nicklaus
M C
MC
Dai
F
F
Ford
H
H
D000243:Adenosine Deaminase / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry*
D001643:Bridged Bicyclo Compounds; D009705:Nucleosides; C046059:bicyclo(3.1.0)hexane; D000243:Adenosine Deaminase