Syntheses of potent Leu-enkephalin analogs possessing beta-hydroxy-alpha,alpha-disubstituted-alpha-amino acid and their characterization to opioid receptors

  • Bioorg Med Chem Lett. 1998 Aug 4;8(15):2027-32. doi: 10.1016/s0960-894x(98)00349-7.
M Horikawa  1 ,  Y Shigeri ,  N Yumoto ,  S Yoshikawa ,  T Nakajima ,  Y Ohfune
Affiliations
  • 1. Suntory Institute for Bioorganic Research, Osaka, Japan.
PMID: 9873480 DOI: 10.1016/s0960-894x(98)00349-7
Abstract

Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-, delta-, and kappa-receptors revealed that [(1R,2S)-Ahh2]Enk (7) was the most potent agonist of delta-opioid receptors among all the synthetic analogs tested, and was 10 times more potent than the native Leu-Enk.