title: "Reverse" carbocyclic fleximers: synthesis of a new class of adenosine deaminase inhibitors.
abstract: A series of flexible carbocyclic pyrimidine nucleosides has been designed and synthesized. In contrast to previously reported "fleximers" from our laboratory, these analogues have the connectivity of the heterocyclic base system "reversed", where the pyrimidine ring is attached to the sugar moiety, rather than the five membered imidazole ring. As was previously seen with the ribose fleximers, their inherent flexibility should allow them to adjust to enzyme binding site mutations, as well as increase the affinity for atypical enzymes. Preliminary biological screening has revealed surprising inhibition of adenosine deaminase, despite their lack of resemblance to adenosine.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore, Maryland 21250, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Zimmermann
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Sadler
authors.forename: Peter I
authors.initials: PI
authors.lastname: O'Daniel
authors.forename: Nathaniel T
authors.initials: NT
authors.lastname: Kim
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Seley-Radtke
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives*; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors / Q000138:chemical synthesis*; D001665:Binding Sites / Q000235:genetics; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D058892:Adenosine Deaminase Inhibitors; D011741:Pyrimidine Nucleosides; D000243:Adenosine Deaminase; D000241:Adenosine