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Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist
Ross, Nicolette C. Kulkarni, Santosh S. McLaughlin, Jay P. Aldrich, Jane V.
Ross, Nicolette C.
Kulkarni, Santosh S.
McLaughlin, Jay P.
Aldrich, Jane V.
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Abstract
The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.; Kojima, Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N. J. Antibiot. (Tokyo) 2002, 55, 847–854.], were synthesized to determine the tryptophan stereochemistry in the natural product. A strategy was developed to select linear precursor peptides that favor cyclization using molecular modeling, and optimized cyclization conditions are reported. The optical rotation of the l-Trp isomer is consistent with that of the natural product. Unexpectedly both isomers exhibit similar nanomolar affinity for KOR.
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Date
2010-09-20
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Elsevier
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Keywords
Cyclic tetrapeptide, Cyclization, Molecular modeling
Citation
Ross, Nicolette C. et al. “Synthesis of CJ-15,208, a Novel Κ-Opioid Receptor Antagonist.” Tetrahedron letters 51.38 (2010): 5020–5023.