2,6-Dimethyltyrosine analogues of a stereodiversified ligand library: Highly potent, selective, non-peptidic μ opioid receptor agonists Journal Article
| Authors: | Harrison, B. A.; Pasternak, G. W.; Verdine, G. L. |
| Article Title: | 2,6-Dimethyltyrosine analogues of a stereodiversified ligand library: Highly potent, selective, non-peptidic μ opioid receptor agonists |
| Abstract: | We recently reported the use of an exhaustively stereodiversified library based on endomorphin-2 (1) to discover μ opioid receptor (MOR) ligands of type 2-4. Here, we report the synthesis and evaluation of 2,6-dimethyltyrosine analogues 5-10. These analogues showed improved affinity for MOR relative to 2-4. In the cases of 5 and 6, we synthesized and evaluated five stereoisomers of each, thereby discovering stereoisomers with unexpected potency, selectivity, and efficacy. These results illustrate the utility of acyclic, stereodiverse libraries. |
| Keywords: | unclassified drug; animals; cerebellum; cell line; drug potency; drug structure; drug screening; drug selectivity; structure-activity relationship; tyrosine; ligands; receptor affinity; ligand binding; mu opiate receptor agonist; receptors, opioid, mu; drug binding; peptide synthesis; stereochemistry; stereoisomerism; peptide library; cricetinae; peptide analysis; binding, competitive; tyrosine derivative; radioligand assay; guinea pigs; humans; article; endomorphin 2; 2,6 dimethyltyrosine derivative |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 46 |
| Issue: | 5 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 2003-02-27 |
| Start Page: | 677 |
| End Page: | 680 |
| Language: | English |
| DOI: | 10.1021/jm025608s |
| PUBMED: | 12593647 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
