269061-41-8Relevant articles and documents
Fluorescent Mu selective opioid ligands from a mixture based cyclic peptide library
Li, Yangmei,Dooley, Colette T.,Misler, Jaime A.,Debevec, Ginamarie,Giulianotti, Marc A.,Cazares, Margaret E.,Maida, Laura,Houghten, Richard A.
, p. 673 - 679 (2013/02/25)
A positional scanning cyclic peptide library was generated using a penta-peptide thioester scaffold. Glycine was fixed at position R1. Diaminopropionic acid was fixed at position R3, with its γ-amino attaching to an anthraniloyl group. Positions R2 and R4 contained 36 l- and d- amino acids and position R5 contained 19 l- amino acids. Cyclization was performed in a mixture of acetonitrile and 1.5 M aqueous imidazole solution (7:1 v/v) at room temperature for 5 days. No significant cross-oligomerization was detected under the cyclization conditions. The library was screened in a binding assay for mu opioid receptor, identifying the active amino acid mixture at each position. A total of 40 individual cyclic peptides were identified and synthesized by the combinations of the most active amino acid mixtures found at three positions 5 × 4 × 2. Two cyclic peptides exhibited high binding affinities to opioid receptor. The most active cyclic peptide in the library was yielded to have Tyr at R2, d-Lys at R4, and Tyr at R5. Further investigation on this compound revealed the side chain-to-tail isomer to have greater binding affinity (14 nM) than the head-to-tail isomer (39 nM). Both isomers were selective for the mu-opioid receptor.
