Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.
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.
Lee
Hyuk Woo
HW
Department of Bioinspired Science, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
Kim
Hea Ok
HO
Choi
Won Jun
WJ
Choi
Sun
S
Lee
Jin Hee
JH
Park
Seul-gi
SG
Yoo
Lena
L
Jacobson
Kenneth A
KA
Jeong
Lak Shin
LS
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*
D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3; D013872:Thionucleosides; C050070:4'-thioadenosine; D000241:Adenosine
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