Studies on the structure-activity relationship of 2',6'-dimethyl-l-tyrosine (Dmt) derivatives: bioactivity profile of H-Dmt-NH-CH(3)

  • Bioorg Med Chem Lett. 2005 Feb 1;15(3):599-602. doi: 10.1016/j.bmcl.2004.11.040.
Yoshio Fujita  1 ,  Yuko Tsuda ,  Takashi Motoyama ,  Tingyou Li ,  Anna Miyazaki ,  Toshio Yokoi ,  Yusuke Sasaki ,  Akihiro Ambo ,  Hideko Niizuma ,  Yunden Jinsmaa ,  Sharon D Bryant ,  Lawrence H Lazarus ,  Yoshio Okada
Affiliations
  • 1. The Graduate School of Food and Medicinal Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan.
PMID: 15664820 DOI: 10.1016/j.bmcl.2004.11.040
Abstract

The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 nM) equal to that of morphine, partial mu-opioid agonism (E(max)=66.6%) in vitro and a moderate antinociception in mice.

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