Browsing by Author "Joung, Misuk"

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    Design, synthesis, and biological evaluation of 5ʹ-deoxy (N)-methanocarbanucleoside derivatives as A3 adenosine receptor ligands
    (Elsevier, 2025) Kim, Minjae; Naik, Siddhi D.; Kim, Seung Woo; Joung, Misuk; Yum, Yun A.; Aswar, Vikas R.; Jeong, Lak Shin
    Based on the potent and selective antagonism exhibited by truncated North (N)-methanocarba adenosine analogs, we synthesized a series of 5ʹ-deoxy (N)-methanocarba nucleosides to explore their structure–activity relationships (SAR). The stereoselective synthesis of the North cyclopropyl-fused alcohol was achieved from d-ribose using ring-closing metathesis, oxidative rearrangement, and cyclopropanation as key steps. Mitsunobu reactions were employed to condense nucleobases with glycosyl donors, followed by N6 functionalization with various amines. Despite their innovative design, all synthesized analogs exhibited lower binding affinity compared to the 4ʹ-thio series and fully truncated (N)-methanocarba adenosine. Docking studies revealed that the 4ʹ-methyl group of the rigid North conformational sugar introduces steric clashes, which likely contribute to the reduced affinity. These findings underscore the critical role of sugar conformation and steric effects in receptor interactions, providing valuable insights for the development of potent and selective A3AR ligands.
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    Synthesis and Biological Evaluation of 5′-Deoxy-adenosine Derivatives as A3 Adenosine Receptor Ligands
    (American Chemical Society, 2025) Kim, Minjae; Naik, Siddhi D.; Choi, Hongseok; Kim, Seung Woo; Park, Jung Hoon; Joung, Misuk; Song, Jiyoon; Gaikwad, Vidyasagar B.; Jeong, Lak Shin
    The A3 Adenosine Receptor (A3AR) is an important therapeutic target due to its role in inflammation and immune response regulation. Herein, we synthesized and evaluated 5′-deoxy-adenosine derivatives with oxygen at the 4′-position, comparing them to previously studied 4′-thionucleosides. Compound 1h exhibited the highest binding affinity (Ki = 5.9 ± 1.1 nM), consistent with the trend observed in the 4′-thionucleosides. Notably, the 5′-deoxy-adenosine derivatives demonstrated enhanced agonistic activity. Docking studies with compound 1h revealed a shift in binding mode when oxygen replaced sulfur at the 4′-position. The compounds retained strong interactions with critical residues, such as Thr94, even without a hydrogen bond donor at the 5′-position. These results explain the increased agonistic effect observed when the ring heteroatom was changed from sulfur to oxygen.