Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers
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- 作者：Jessica H. Harvey ; Darcie H. Long ; Pamela M. England ; Jennifer L. Whistler
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：August 9, 2012
- 年：2012
- 卷：3
- 期：8
- 页码：640-644
- 全文大小：320K
- 年卷期：v.3,no.8(August 9, 2012)
- ISSN：1948-5875
文摘
Opioid receptors, including the 渭- and 未-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with 鈥渢uned affinity鈥?at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.