title: Conformationally restricted nucleosides. The reaction of adenosine deaminase with substrates built on a bicyclo[3.1.0]hexane template.
abstract: 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.
authors.affiliation: Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: V E
authors.initials: VE
authors.lastname: Marquez
authors.forename: P
authors.initials: P
authors.lastname: Russ
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: K J
authors.initials: KJ
authors.lastname: Shin
authors.forename: C
authors.initials: C
authors.lastname: George
authors.forename: M C
authors.initials: MC
authors.lastname: Nicklaus
authors.forename: F
authors.initials: F
authors.lastname: Dai
authors.forename: H
authors.initials: H
authors.lastname: Ford
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000737:chemistry*
chemical_list: D001643:Bridged Bicyclo Compounds; D009705:Nucleosides; C046059:bicyclo(3.1.0)hexane; D000243:Adenosine Deaminase