title: Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.
abstract: We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine receptor. However, all homologated nucleosides were devoid of binding affinity at all subtypes of adenosine receptors, indicating that free rotation through the single bond allowed the compound to adopt an indefinite number of conformations, disrupting the favorable binding interaction essential for receptor recognition.
authors.affiliation: Department of Bioinspired Science, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Hyuk Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Choi
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Seul-gi
authors.initials: SG
authors.lastname: Park
authors.forename: Lena
authors.initials: L
authors.lastname: Yoo
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D043684:Receptor, Adenosine A3 / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine
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