Standard

Development and in vitro characterization of neuromedin U analogues. / De Prins, An; Betti, Cecilia; Sivertsen, Bjorn; Caveliers, Vicky; Van Eeckhaut, Ann; Holst, Birgitte; Ballet, Steven; Smolders, Ilse Julia.

2016. Poster session presented at Belgian Peptide Group Meeting 2016, Brussels, Belgium.

Research output: Unpublished contribution to conferencePoster

Harvard

De Prins, A, Betti, C, Sivertsen, B, Caveliers, V, Van Eeckhaut, A, Holst, B, Ballet, S & Smolders, IJ 2016, 'Development and in vitro characterization of neuromedin U analogues', Belgian Peptide Group Meeting 2016, Brussels, Belgium, 17/02/16 - 18/02/16.

APA

De Prins, A., Betti, C., Sivertsen, B., Caveliers, V., Van Eeckhaut, A., Holst, B., ... Smolders, I. J. (2016). Development and in vitro characterization of neuromedin U analogues. Poster session presented at Belgian Peptide Group Meeting 2016, Brussels, Belgium.

Vancouver

De Prins A, Betti C, Sivertsen B, Caveliers V, Van Eeckhaut A, Holst B et al. Development and in vitro characterization of neuromedin U analogues. 2016. Poster session presented at Belgian Peptide Group Meeting 2016, Brussels, Belgium.

Author

De Prins, An ; Betti, Cecilia ; Sivertsen, Bjorn ; Caveliers, Vicky ; Van Eeckhaut, Ann ; Holst, Birgitte ; Ballet, Steven ; Smolders, Ilse Julia. / Development and in vitro characterization of neuromedin U analogues. Poster session presented at Belgian Peptide Group Meeting 2016, Brussels, Belgium.

BibTeX

@conference{ad54db59486e4052b5b965461b7701fc,
title = "Development and in vitro characterization of neuromedin U analogues",
abstract = "Chronic stress is a predominant risk factor for a variety of psychiatric and neurological disorders such as depression, anxiety and epilepsy. Endogenous systems which regulate the stress response are interesting tartgets for the development of novel treatments for these disorders. In this study we focus on neuromedin U (NMU), a neuropeptide regulator of the stress response via top-down control of the hypothalamus-pituitary-adrenal axis. NMU exerts its biological effects via two G-protein-coupled receptors, NMUR1 and NMUR2. NMUR1 is mostly found in the periphery whereas NMUR2, the receptor of our interest, is most abundant in the central nervous system (Brighton et al, 2004). The purpose of this study is to develop new peptidergic selective NMUR2 antagonists which are enzymatically stable and blood-brain-barrier (BBB) permeable.NMU-8 (H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2), a natural occuring form of NMU, is taken as lead molecule for the synthesis of new analogues. The NMU-ligands are synthesized via solid phase peptide synthesis under classical conditions on rink amide polystyrene resin. A first batch of analogues is prepared on basis of the available structure-activity relationships. Mainly two types of modifications are performed, namely chirality switches and the introduction of different N-capping groups. The in vitro characterization of these peptides is performed by an inositol phosphate accumulation assay.The results of this in vitro characterization present EC50 values of a similar magnitude as NMU-8. Moreover our experiments revealed that acetylation of the N-terminus leads in general to an increase of the relative activity compared to the non-acetylated ligand. This first generation of NMU analogues includes peptides which could possibly act as antagonists on both NMURs, as no inositol accumulation was detected up to 10-6M. On basis of the performed assay it cannot be concluded that antagonism is indeed present. Some peptides of the first generation of NMU analogues are partial agonists for both NMURs, certain amongst them with EC50 values of comparable magnitude as NMU-8.Further research is needed to synthesize a NMUR2 selective, enzymatically stable and BBB permeable ligand.",
keywords = "Neuromedin U, stress response, solid phase peptide synthesis, inositol phosphate accumulation assay",
author = "{De Prins}, An and Cecilia Betti and Bjorn Sivertsen and Vicky Caveliers and {Van Eeckhaut}, Ann and Birgitte Holst and Steven Ballet and Smolders, {Ilse Julia}",
year = "2016",
month = "2",
day = "17",
language = "English",
note = "Belgian Peptide Group Meeting 2016 ; Conference date: 17-02-2016 Through 18-02-2016",

}

RIS

TY - CONF

T1 - Development and in vitro characterization of neuromedin U analogues

AU - De Prins, An

AU - Betti, Cecilia

AU - Sivertsen, Bjorn

AU - Caveliers, Vicky

AU - Van Eeckhaut, Ann

AU - Holst, Birgitte

AU - Ballet, Steven

AU - Smolders, Ilse Julia

PY - 2016/2/17

Y1 - 2016/2/17

N2 - Chronic stress is a predominant risk factor for a variety of psychiatric and neurological disorders such as depression, anxiety and epilepsy. Endogenous systems which regulate the stress response are interesting tartgets for the development of novel treatments for these disorders. In this study we focus on neuromedin U (NMU), a neuropeptide regulator of the stress response via top-down control of the hypothalamus-pituitary-adrenal axis. NMU exerts its biological effects via two G-protein-coupled receptors, NMUR1 and NMUR2. NMUR1 is mostly found in the periphery whereas NMUR2, the receptor of our interest, is most abundant in the central nervous system (Brighton et al, 2004). The purpose of this study is to develop new peptidergic selective NMUR2 antagonists which are enzymatically stable and blood-brain-barrier (BBB) permeable.NMU-8 (H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2), a natural occuring form of NMU, is taken as lead molecule for the synthesis of new analogues. The NMU-ligands are synthesized via solid phase peptide synthesis under classical conditions on rink amide polystyrene resin. A first batch of analogues is prepared on basis of the available structure-activity relationships. Mainly two types of modifications are performed, namely chirality switches and the introduction of different N-capping groups. The in vitro characterization of these peptides is performed by an inositol phosphate accumulation assay.The results of this in vitro characterization present EC50 values of a similar magnitude as NMU-8. Moreover our experiments revealed that acetylation of the N-terminus leads in general to an increase of the relative activity compared to the non-acetylated ligand. This first generation of NMU analogues includes peptides which could possibly act as antagonists on both NMURs, as no inositol accumulation was detected up to 10-6M. On basis of the performed assay it cannot be concluded that antagonism is indeed present. Some peptides of the first generation of NMU analogues are partial agonists for both NMURs, certain amongst them with EC50 values of comparable magnitude as NMU-8.Further research is needed to synthesize a NMUR2 selective, enzymatically stable and BBB permeable ligand.

AB - Chronic stress is a predominant risk factor for a variety of psychiatric and neurological disorders such as depression, anxiety and epilepsy. Endogenous systems which regulate the stress response are interesting tartgets for the development of novel treatments for these disorders. In this study we focus on neuromedin U (NMU), a neuropeptide regulator of the stress response via top-down control of the hypothalamus-pituitary-adrenal axis. NMU exerts its biological effects via two G-protein-coupled receptors, NMUR1 and NMUR2. NMUR1 is mostly found in the periphery whereas NMUR2, the receptor of our interest, is most abundant in the central nervous system (Brighton et al, 2004). The purpose of this study is to develop new peptidergic selective NMUR2 antagonists which are enzymatically stable and blood-brain-barrier (BBB) permeable.NMU-8 (H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg-Asn-NH2), a natural occuring form of NMU, is taken as lead molecule for the synthesis of new analogues. The NMU-ligands are synthesized via solid phase peptide synthesis under classical conditions on rink amide polystyrene resin. A first batch of analogues is prepared on basis of the available structure-activity relationships. Mainly two types of modifications are performed, namely chirality switches and the introduction of different N-capping groups. The in vitro characterization of these peptides is performed by an inositol phosphate accumulation assay.The results of this in vitro characterization present EC50 values of a similar magnitude as NMU-8. Moreover our experiments revealed that acetylation of the N-terminus leads in general to an increase of the relative activity compared to the non-acetylated ligand. This first generation of NMU analogues includes peptides which could possibly act as antagonists on both NMURs, as no inositol accumulation was detected up to 10-6M. On basis of the performed assay it cannot be concluded that antagonism is indeed present. Some peptides of the first generation of NMU analogues are partial agonists for both NMURs, certain amongst them with EC50 values of comparable magnitude as NMU-8.Further research is needed to synthesize a NMUR2 selective, enzymatically stable and BBB permeable ligand.

KW - Neuromedin U

KW - stress response

KW - solid phase peptide synthesis

KW - inositol phosphate accumulation assay

M3 - Poster

ER -

ID: 23935215