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Issue 6, 2014
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N1-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors

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Abstract

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.

Graphical abstract: N1-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors

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Supplementary files

Article information


Submitted
23 Feb 2014
Accepted
04 Apr 2014
First published
04 Apr 2014

Med. Chem. Commun., 2014,5, 792-796
Article type
Concise Article

N1-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors

A. Journé, S. A. M. Habib, B. R. Dodda, M. N. F. Morcos, M. S. Sadek, S. A. A. Tadros, P. A. Witt-Enderby, R. Jockers and D. P. Zlotos, Med. Chem. Commun., 2014, 5, 792
DOI: 10.1039/C4MD00079J

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