The C-terminal pentapeptide acein analogue (JMV3315) stimulates dopamine release in the brain
Charlène Lucas-Valmalle A , Gilles Subra A , Pascal Verdié A , Marie-Lou Kemel B , Valérie Daugé C , Karine Puget A D and Jean Martinez
A *
+ Author Affiliations
- Author Affiliations
A Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-Université Montpellier-ENSCM, Pôle Chimie Balard Recherche, 1919, route de Mende, 34293 Montpellier cedex 5, France.
B CIRB, Collège de France, 11, place Marcelin Berthelot, 75231 Paris Cedex 05, France.
C INSERM, UMR 952, Physiopathologie des Maladies du Système Nerveux Central, 9 Quai Saint Bernard, F-75005 Paris, France.
D Present address: GENEPEP PEPTIDES, 12 rue du fer á cheval, 34430 Saint Jean de Védas, France.
Australian Journal of Chemistry 76(8) 448-454 https://doi.org/10.1071/CH22232
Submitted: 8 November 2022 Accepted: 23 February 2023 Published: 31 May 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing.
Abstract
We have previously reported the synthesis and biological activity of a newly identified peptide of sequence H–Pro–Pro–Thr–Thr–Thr–Lys–Phe–Ala–Ala–OH called acein that is able to stimulate dopamine release in the brain of rodents in vivo and ex vivo by interacting with angiotensin converting enzyme (ACE). In the present piece of work, we studied the structure–activity relationships of acein using displacement experiments of the labelled ligand [125I]Tyr–Pro–Pro–Thr–Thr–Thr–Lys–Phe–Ala–Ala–OH on guinea pig brain membranes, known to have high-affinity acein binding sites. We determined that the C-terminal pentapeptide H–Thr–Lys–Phe–Ala–Ala–OH is the minimal structure able to interact with high affinity (Ki (inhibitory constant) 13 ± 2 nM) with acein binding sites. Among the analogues of the pentapeptide that were synthesized, the pentapeptide H–Thr–Lys–Tyr–Ala–Ala–OH showed the highest affinity (Ki 3.7 ± 1.0 nM). Accordingly, this pentapeptide was able to stimulate dopamine release from striatal slices taken from the sensorimotor territory of rats.
Keywords: acein, angiotensin converting enzyme, biological activity, central nervous system, dopamine, enzyme, peptides, structure–activity relationships.
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