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Abstract
In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr- d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3′,5′-(CF 3) 2Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr- cyclo[ d-Cys-Gly-Phe-Met-Pro- d-Cys]-Trp-NH-[3′,5′-(CF 3) 2Bzl]) was found as a highly selective δ opioid agonist over μ receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24 h half life in rat plasma.
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