科研之友
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摘要
A novel series of dimeric melatonin analogues obtained by connecting two melatonin molecules through N1 with spacers of 15-24 atoms was synthesized and characterized in 2-[(125)-I]-iodomelatonin binding and bioluminescence resonance energy transfer (BRET) experiments at MT1 and MT2 receptors. Compounds 4 (16 atoms spacer) and 13 (24 atoms spacer) are among the ligands inducing the maximal BRET at MT2-homodimers as well as at both types of MT1/MT2 heterodimers. Notably, ligand-induced BRET changes observed for compounds linked through spacers of 22-24 atoms could be attributed to ligand-induced conformational changes between the two protomers of MT1 and MT2 homo-and heterodimers providing evidence for the binding of both pharmacophores of dimeric melatonin analogues to the two protomers of receptor dimers.
- 出版日期2014-6
