Design, synthesis, and binding of homologated truncated 4′-thioadenosine derivatives at the human A3 adenosine receptors

Hyuk Woo Lee, Hea Ok Kim, Won Jun Choi, Sun Choi, Jin Hee Lee, Seul Gi Park, Lena Yoo, Kenneth A. Jacobson, Lak Shin Jeong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

We synthesized homologated truncated 4′-thioadenosine analogues 3 in which a methylene (CH2) group was inserted in place of the glycosidic bond of a potent and selective A3 adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A3 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.

Original languageEnglish
Pages (from-to)7015-7021
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number19
DOIs
StatePublished - 1 Oct 2010

Bibliographical note

Funding Information:
This work was supported by the grant from the Korea Research Foundation ( NRF-2008-314-E00304 ) and the NIDDK Intramural Research Program . H.W.L. acknowledges the research professor fellowship from the Ewha Womans University (2009).

Keywords

  • A adenosine receptor
  • Binding affinity
  • Homologation
  • Truncated 4′-thioadenosine

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