Solution structures and molecular interactions of selective melanocortin receptor antagonists

Chul Jin Lee, Ji Hye Yun, Sung Kil Lim, Weontae Lee

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


The solution structures and inter-molecular interaction of the cyclic melanocortin antagonists SHU9119, JKC363, HS014, and HS024 with receptor molecules have been determined by NMR spectroscopy and molecular modeling. While SHU9119 is known as a nonselective antagonist, JKC363, HS014, and HS024 are selective for the melanocortin subtype-4 receptor (MC4R) involved in modulation of food intake. Data from NMR and molecular dynamics suggest that the conformation of the Trp9 sidechain in the three MC4R-selective antagonists is quite different from that of SHU9119. This result strongly supports the concept that the spatial orientation of the hydrophobic aromatic residue is more important for determining selectivity than the presence of a basic, "arginine-like" moiety responsible for biological activity. We propose that the conformation of hydrophobic residues of MCR antagonists is critical for receptor-specific selectivity.

Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalMolecules and cells
Issue number6
Publication statusPublished - 2010 Dec

Bibliographical note

Funding Information:
The World Class University program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R33-2009-000-10123-0) supported this research. This research was partially supported by a Brain Korea (BK) project. We would like to thank Professor Kurt Wüthrich for fruitful discussion.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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