Fluorescent Mu selective opioid ligands from a mixture based cyclic peptide library Article

Li, Y, Dooley, CT, Misler, JA et al. (2012). Fluorescent Mu selective opioid ligands from a mixture based cyclic peptide library . 14(12), 673-679. 10.1021/co300110t

cited authors

  • Li, Y; Dooley, CT; Misler, JA; Debevec, G; Giulianotti, MA; Cazares, ME; Maida, L; Houghten, RA

authors

abstract

  • 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. © 2012 American Chemical Society.

publication date

  • December 10, 2012

Digital Object Identifier (DOI)

start page

  • 673

end page

  • 679

volume

  • 14

issue

  • 12