The GP2A European Conference is a two-day meeting focused on medicinal chemistry and the use of tools to explore all fields of drug discovery and drug design such as molecular modelling, bioorganic chemistry, MS studies, in vitro in vivo assays, and structure activity relationships. Abstracts of keynote lectures, plenary lectures, junior lectures, flash presentations, and posters presented during the meeting are collated in this report.

Fluorescent melatoninergic ligands have been designed by associating the 4-azamelatonin ligands with different fluorophores. The ligands show good affinities for MT1 and/or MT2 receptors and substitution of the fluorophore at positions 2 or 5 of the azamelatonin core had a direct impact on the MT receptors selectivity while grafting the fluorophores on position N1 produced fluorescent ligands with good affinities for both MT1/MT2 receptors. The optimal position N-1, C-2 or C-5 on the 4-azamelatonin ligand appeared strongly dependent upon the nature of the fluorophore itself.

Fluorescent melatoninergic ligands have been designed by associating the 4-azamelatonin ligands with different fluorophores.

Background and purpose:For many years, it was suspected that sheep expressed only one melatonin receptor (closely resembling MT1 from other mammal species). Here we report the cloning of another melatonin receptor, MT2, from sheep.Experimental approach:Using a thermo-resistant reverse transcriptase and polymerase chain reaction primer set homologous to the bovine MT2 mRNA sequence, we have cloned and characterized MT2 receptors from sheep retina.Key results:The ovine MT2 receptor presents 96%, 72% and 67% identity with cattle, human and rat respectively. This MT2 receptor stably expressed in CHO-K1 cells showed high-affinity 2[125I]-iodomelatonin binding (K-D = 0.04 nM). The rank order of inhibition of 2[125I]-iodomelatonin binding by melatonin, 4-phenyl-2-propionamidotetralin and luzindole was similar to that exhibited by MT2 receptors of other species (melatonin > 4-phenyl-2-propionamidotetralin > luzindole). However, its pharmacological profile was closer to that of rat, rather than human MT2 receptors. Functionally, the ovine MT2 receptors were coupled to G(i) proteins leading to inhibition of adenylyl cyclase, as the other melatonin receptors. In sheep brain, MT2 mRNA was expressed in pars tuberalis, choroid plexus and retina, and moderately in mammillary bodies. Real-time polymerase chain reaction showed that in sheep pars tuberalis, premammillary hypothalamus and mammillary bodies, the temporal pattern of expression of MT1 and MT2 mRNA was not parallel in the three tissues.Conclusion and implications:Co-expression of MT1 and MT2 receptors in all analysed sheep brain tissues suggests that MT2 receptors may participate in melatonin regulation of seasonal anovulatory activity in ewes by modulating MT1 receptor action.