title: Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist.
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.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
authors.forename: Nicolette C
authors.initials: NC
authors.lastname: Ross
authors.forename: Santosh S
authors.initials: SS
authors.lastname: Kulkarni
authors.forename: Jay P
authors.initials: JP
authors.lastname: McLaughlin
authors.forename: Jane V
authors.initials: JV
authors.lastname: Aldrich