Ross, Nicolette C.Kulkarni, Santosh S.McLaughlin, Jay P.Aldrich, Jane V.2017-04-192017-04-192010-09-20Ross, Nicolette C. et al. “Synthesis of CJ-15,208, a Novel Κ-Opioid Receptor Antagonist.” Tetrahedron letters 51.38 (2010): 5020–5023.https://hdl.handle.net/1808/23743The 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.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.http://creativecommons.org/licenses/by-nc-nd/3.0/Cyclic tetrapeptideCyclizationMolecular modelingArticle10.1016/j.tetlet.2010.07.086openAccess