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Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show in Vitro Kappa and Mu Opioid Receptor Agonism.

ABSTRACT: The dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold was originally developed in the production of selective delta opioid receptor (DOR) antagonists. Installation of a 7-benzyl pendant on the tetrahydroisoquinoline core of this classic opioid scaffold introduced kappa opioid receptor (KOR) agonism. Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment of cocaine addiction.

SUBMITTER: Montgomery D

PROVIDER: S-EPMC6726392 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show <i>in Vitro</i> Kappa and Mu Opioid Receptor Agonism.

Montgomery Deanna D Anand Jessica P JP Griggs Nicholas W NW Fernandez Thomas J TJ Hartman Joshua G JG Sánchez-Santiago Ashley A AA Pogozheva Irina D ID Traynor John R JR Mosberg Henry I HI

ACS chemical neuroscience 20190701 8

The dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold was originally developed in the production of selective delta opioid receptor (DOR) antagonists. Installation of a 7-benzyl pendant on the tetrahydroisoquinoline core of this classic opioid scaffold introduced kappa opioid receptor (KOR) agonism. Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in th ...[more]

PMID: 31199621

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Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors.

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