Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[ d -Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation Article

Li, Y, Cazares, M, Wu, J et al. (2016). Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[ d -Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation . JOURNAL OF MEDICINAL CHEMISTRY, 59(3), 1239-1245. 10.1021/acs.jmedchem.5b01899

cited authors

  • Li, Y; Cazares, M; Wu, J; Houghten, RA; Toll, L; Dooley, C

authors

abstract

  • To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[d-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe3 was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at d-Lys2-Xxx3 is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

publication date

  • February 11, 2016

published in

Digital Object Identifier (DOI)

start page

  • 1239

end page

  • 1245

volume

  • 59

issue

  • 3