Bio: Steven Ballet is Full Professor at Vrije Universiteit Brussel (VUB, Brussels, Belgium). He completed his PhD at the Vrije Universiteit Brussel in 2007. During his PhD formation, he was submerged in the magical world of peptides and peptidomimetics and specialized in the synthesis of conformationally constrained amino acids. Directly following his PhD training, he went for a first postdoctoral stay in Australia at the University of Adelaide with Professor Andrew Abell. During his second postdoctoral position at the Institut de Recherches Cliniques de Montréal (Canada), he conducted research on opioid peptides, designing molecules that interact with opioid receptors and other neural targets. Since 2010, Professor Ballet has served as Head of the Research Group of Organic Chemistry within the Departments of Chemistry and Bioengineering Sciences at his alma mater, the Vrije Universiteit Brussel. His main area of research focuses on the peptide and peptidomimetic compound and their applications in medicinal chemistry and biomaterial development.

Abstract: The alleviation or treatment of moderate to severe pain states commonly invokes the use of opioids. Unfortunately, their chronic administration induces various undesirable side effects. One strategy to overcome these major side effects and to prolong the antinociceptive efficiency of the applied drugs involves the creation of multifunctional compounds which contain hybridized structures. Opioids have also been combined with non-opioid bioactive neurotransmitters and peptide hormones that are involved in pain perception.1 Such novel chimeras, may interact independently with their respective receptors and potentially result in more effective antinociceptive properties. The designed multiple ligands presented in this work include peptide-based opioid-non-opioid dimer analogs, such as for example opioid-neurokinin 1 receptor,2 opioid-nociceptin3 and opioid-neuropeptide FF DMLs.4 Some of the prepared ligands demonstrated to be dually effective in both acute and neuropathic pain models. Gratifyingly, compounds with reduced analgesic (cross-) tolerance (with morphine), physical dependence, and respiratory depression were discovered. Additionally, another type of hybridization will be presented: a fusion between opioid pharmacophores and hydrogel-forming hexapeptide sequences. While the above opioid pharmacophores induce analgesic effects up to 8 hours post injection, fusion with self-assembling hexapeptide sequences allowed formation of injectable hydrogels, which slowly degrade subcutaneously after injection. This innovative controlled-drug delivery method gave antinociceptive effects of 72 - 96h.5 

References: 1- Breault et al. Pharmacol. Res. 2024, 209, 107408 ; 2- Guillemyn, K. et al. Eur. J. Med. Chem. 2015, 92, 64 ; 3- Guillemyn, K. et al. J. Med. Chem. 2016, 59, 3777 ; 4- Drieu la Rochelle, A. et al. Pain 2018, 159, 1705 ; 5- Martin, C. et al. J. Med. Chem. 2018, 61, 9784.