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Marceau Philippe


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tél : 02.38.25.51.08 - fax : 02.38.25.55.83

Publications

2015   Références trouvées : 1

Beltramo, M., Robert, V., Galibert, M., Madinier, J.-B., Marceau, P., Dardente, H., Decourt, C., De Roux, N., Lomet, D., Delmas, A. F., Caraty, A. and Aucagne, V.  (2015)

Rational Design of Triazololipopeptides Analogs of Kisspeptin Inducing a Long-Lasting Increase of Gonadotropins

Journal of Medicinal Chemistry (2015) 58 (8) 3459-3470 - doi : 10.1021/jm5019675
New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo–pituitary–gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism.

New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo–pituitary–gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism.


2012   Références trouvées : 2

Aucagne, V., Valverde, I.E., Marceau, P., Galibert, M., Dendane, N., Delmas, A.F.  (2012)

Towards the Simplification of Protein Synthesis : Iterative Solid-Supported Ligations with Concomitant Purifications

Angewandte Chemie International Edition, 51 (45) 11320-11324
Please release me : A new linker for the temporary tagging of peptides at their N-terminus after solid-phase elongation, and its potential for capture/release purification is demonstrated. This concept is extended to a remarkably efficient self-purifying N-to-C iterative triazole ligation strategy, which is applied to the synthesis of a polypeptide having 160 residues, in a high purity without the need for chromatographic purification (see picture ; orange blocks : peptide segments).

Please release me : A new linker for the temporary tagging of peptides at their N-terminus after solid-phase elongation, and its potential for capture/release purification is demonstrated. This concept is extended to a remarkably efficient self-purifying N-to-C iterative triazole ligation strategy, which is applied to the synthesis of a polypeptide having 160 residues, in a high purity without the need for chromatographic purification (see picture ; orange blocks : peptide segments).

Buré, C., Marceau, P., Meudal, H. and Delmas, A.F.  (2012)

Synthesis and analytical investigation of C-terminally modified peptide aldehydes and ketone : application to oxime ligation

Journal of Peptide Science 18 (3) 147-154
C-terminally modified peptides aldehyde (glycinal and alpha-oxo aldehyde peptides) and ketone (pyruvic acid-containing

peptide) were synthesised to get new insights into the mechanism of acido-catalysed oxime ligation. Their tetrahedral

hydrated forms were investigated in solution and in the gas phase, using NMR and in-source collision-induced dissociation mass

spectrometry, respectively, and the kinetics of the oximation reactions followed using analytical HPLC. The results obtained confirmed

that the first step of the oximation reaction was the limiting step for the pyruvic acid-containing peptides because of the

steric effect and of the carbon angular strain of the ketone. The second step is the determining step for the aldehyde peptides

because the basicity of the oxygen of the hydroxyl function of the tetrahedral form is greater for glycinal than for alpha-oxo

aldehyde. These data strongly suggest that the hydrated form of the aldehyde partner has to be considered when oxime

reactions are performed in aqueous buffer.

C-terminally modified peptides aldehyde (glycinal and alpha-oxo aldehyde peptides) and ketone (pyruvic acid-containing
peptide) were synthesised to get new insights into the mechanism of acido-catalysed oxime ligation. Their tetrahedral
hydrated forms were investigated in solution and in the gas phase, using NMR and in-source collision-induced dissociation mass
spectrometry, respectively, and the kinetics of the oximation reactions followed using analytical HPLC. The results obtained confirmed
that the first step of the oximation reaction was the limiting step for the pyruvic acid-containing peptides because of the
steric effect and of the carbon angular strain of the ketone. The second step is the determining step for the aldehyde peptides
because the basicity of the oxygen of the hydroxyl function of the tetrahedral form is greater for glycinal than for alpha-oxo
aldehyde. These data strongly suggest that the hydrated form of the aldehyde partner has to be considered when oxime
reactions are performed in aqueous buffer.


2005   Références trouvées : 1

Marceau, P ; Bure, C ; Delmas, AF  (2005)

Efficient synthesis of C-terminal modified peptide ketones for chemical ligations

Bioorganic & Medicinal Chemistry Letters 15 (24) 5442-5445
Synthesis of a C-terminal modified peptide with an a-amido methylketone was efficiently carried out using a backbone-amide-type linker loading with a monofunctionalized diamine, provided that no base such as piperidine or diisopropylethylamine or a reducing agent such as triisopopylsilane was used for the synthetic pathway. The ketoxime-forming chemoselective ligation between a methylketone and an aminooxy was quantitative in 5 h at pH 2. (c) 2005 Elsevier Ltd. All rights reserved.

Synthesis of a C-terminal modified peptide with an a-amido methylketone was efficiently carried out using a backbone-amide-type linker loading with a monofunctionalized diamine, provided that no base such as piperidine or diisopropylethylamine or a reducing agent such as triisopopylsilane was used for the synthetic pathway. The ketoxime-forming chemoselective ligation between a methylketone and an aminooxy was quantitative in 5 h at pH 2. (c) 2005 Elsevier Ltd. All rights reserved.


2003   Références trouvées : 1

Frison, N ; Meunier, L ; Marceau, P ; Quetard, C ; Strecker, G ; Roche, AC ; Mayer, R ; Monsigny, M  (2003)

Chromatographic separation of Lewis a and Lewis x oligosaccharides as glycosynthons

Biochimie 85 (1-2) 47-51
Lewis a and Lewis x oligosaccharides Galbeta3(Fucalpha4)GlcNAcbeta3Galbeta4Glc and Galbeta4(Fucalpha3)GlcNAcbeta3Galbeta4Glc are easily isolated as a mixture from biological fluids, including human milk. However, because they behave almost identically in most chromatographic systems, it is difficult to have each of them as a pure compound. Incidentally, we found that they were easily separated by HPLC as glycosynthons [Galbeta3(Fucalpha4)GlcNAcbeta3Galbeta4Glc-Glp-betaAla-OBzl and Galbeta4(Fucalpha3)GlcNAcbeta3Galbeta4Glc-Glp-betaAla-OBzl] after substitution of the terminal reducing sugar by a short peptide (pyroglutamyl-betaalanyl-O-benzyl ester) in a one-pot two-step reaction (Carbohydr. Lett. 1 (1995) 269 ; Bioconjug. Chem. 9 (1998) 268).

Lewis a and Lewis x oligosaccharides Galbeta3(Fucalpha4)GlcNAcbeta3Galbeta4Glc and Galbeta4(Fucalpha3)GlcNAcbeta3Galbeta4Glc are easily isolated as a mixture from biological fluids, including human milk. However, because they behave almost identically in most chromatographic systems, it is difficult to have each of them as a pure compound. Incidentally, we found that they were easily separated by HPLC as glycosynthons [Galbeta3(Fucalpha4)GlcNAcbeta3Galbeta4Glc-Glp-betaAla-OBzl and Galbeta4(Fucalpha3)GlcNAcbeta3Galbeta4Glc-Glp-betaAla-OBzl] after substitution of the terminal reducing sugar by a short peptide (pyroglutamyl-betaalanyl-O-benzyl ester) in a one-pot two-step reaction (Carbohydr. Lett. 1 (1995) 269 ; Bioconjug. Chem. 9 (1998) 268).


2002   Références trouvées : 1

Frison, N ; Marceau, P ; Roche, AC ; Monsigny, M ; Mayer, R  (2002)

Oligolysine-based saccharide clusters : synthesis and specificity

Biochemical Journal 368 111-119 Part 1
In search of specific and highly selective sugar clusters for cell receptors, such as membrane lectins, various disaccharides were coupled to small peptide cores through an amide bond. In a first step, the reducing disaccharides, i.e. lactose and three different dimannoses, were converted into glycosyl-pyroglutamyl-ß-alanine derivatives. The free carboxylic group of these conjugates was then coupled to the a and epsilon amino groups of the core peptide (Lys(n)-Ala-Cys-NH2) with n = 1 to 5, with complete substitution leading to homogeneous glycoclusters. The thiol group of the cysteine residue was used to tag the glycosylated oligolysines upon reaction with fluorescein iodoacetamide. The affinity of these glycoclusters towards two plant lectins was assessed by surface plasmon resonance. The selectivity of their cell uptake was investigated by flow cytometry using two types of cells : a human hepatoma cell line (HepG2 cells) expressing the plasma membrane galactose-specific lectin, and monocyte-derived dendritic cells expressing the plasma membrane mannose-specific lectin. The glycoclusters containing four or five disaccharides were shown to bind plant lectins and cell surface membrane lectins with a narrow selectivity and with a high affinity.

In search of specific and highly selective sugar clusters for cell receptors, such as membrane lectins, various disaccharides were coupled to small peptide cores through an amide bond. In a first step, the reducing disaccharides, i.e. lactose and three different dimannoses, were converted into glycosyl-pyroglutamyl-ß-alanine derivatives. The free carboxylic group of these conjugates was then coupled to the a and epsilon amino groups of the core peptide (Lys(n)-Ala-Cys-NH2) with n = 1 to 5, with complete substitution leading to homogeneous glycoclusters. The thiol group of the cysteine residue was used to tag the glycosylated oligolysines upon reaction with fluorescein iodoacetamide. The affinity of these glycoclusters towards two plant lectins was assessed by surface plasmon resonance. The selectivity of their cell uptake was investigated by flow cytometry using two types of cells : a human hepatoma cell line (HepG2 cells) expressing the plasma membrane galactose-specific lectin, and monocyte-derived dendritic cells expressing the plasma membrane mannose-specific lectin. The glycoclusters containing four or five disaccharides were shown to bind plant lectins and cell surface membrane lectins with a narrow selectivity and with a high affinity.


2001   Références trouvées : 1

Bedouet, L ; Bousser, MT ; Frison, N ; Boccaccio, C ; Abastado, JP ; Marceau, P ; Mayer, R ; Monsigny, M ; Roche, AC  (2001)

Uptake of dimannoside clusters and oligomannosides by human dendritic cells

Bioscience Reports 21 (6) 839-855
Knowing that human blood monocyte-derived dendritic cells express cell-surface mannose-specific lectins, we prepared various mannoses containing glycoconjugates with the aim of developing highly specific synthetic carriers of oligonucleotides and genes. Conjugates were prepared from oligosaccharides obtained by hydrazinolysis of Saccharomyces cerevisiae invertase glycopeptides.

Knowing that human blood monocyte-derived dendritic cells express cell-surface mannose-specific lectins, we prepared various mannoses containing glycoconjugates with the aim of developing highly specific synthetic carriers of oligonucleotides and genes. Conjugates were prepared from oligosaccharides obtained by hydrazinolysis of Saccharomyces cerevisiae invertase glycopeptides.


1991   Références trouvées : 1

Marceau, P ; Gautreau, L ; Beguin, F ; Guillaumet, G  (1991)

Graphite intercalation compounds as precursors of activated metals : Synthesis of ß, gamma -unsaturated ketones through condensation of allylic organozinc derivatives with nitriles

Journal of Organometallic Chemistry 403 (1-2)
Zinc supported on graphite (Zn-0/Gr) prepared from the binary KC8 grahite interaculation compound was used as metallic reagent for the synthesis of various ß-gamma -unsaturated ketones from nitriles and a allylic halide. In aromatic series, the reaction is not influenced by the groups present on the ring of the nitrile. The most striking feature of the reaction is that the chloro and bromo parent reagents have comparable reactivities ; this is attributed to the fact that the reaction of the activated organozinc derivative with the nitrile takes place on the surface of the carbonaceous support rather than in the solution.

Zinc supported on graphite (Zn-0/Gr) prepared from the binary KC8 grahite interaculation compound was used as metallic reagent for the synthesis of various ß-gamma -unsaturated ketones from nitriles and a allylic halide. In aromatic series, the reaction is not influenced by the groups present on the ring of the nitrile. The most striking feature of the reaction is that the chloro and bromo parent reagents have comparable reactivities ; this is attributed to the fact that the reaction of the activated organozinc derivative with the nitrile takes place on the surface of the carbonaceous support rather than in the solution.


1988   Références trouvées : 1

Marceau, P ; Beguin, F ; Guillaumet, G  (1988)

Les composés d’insertion du graphite comme précurseurs de métaux finement divisés. I : Couplage d’halogénures benzyliques

Journal of Organometallic Chemistry 342 137-141
Préparation d'un réactif sélectif et doux pour le couplage du chlorure de benzyle. Toutefois l'utilisation d'agrégats bimétalliques Ni-Cu permet d'améliorer la sélectivité et le rendement en produit de duplication.

Préparation d’un réactif sélectif et doux pour le couplage du chlorure de benzyle. Toutefois l’utilisation d’agrégats bimétalliques Ni-Cu permet d’améliorer la sélectivité et le rendement en produit de duplication.


1984   Références trouvées : 1

Béguin, F ; Marceau, P ; Setton, R  (1984)

Stoichiometry and interlayer structure of the KC24s (THF)m graphitides (with s = 1,2 or 3)

Carbon 22 218


1983   Références trouvées : 1

Béguin, F ; Estrade-Szwarckopf, H ; Conard, J ; Lauginie, P ; Marceau, P ; Guérard, D ; Facchini, L   (1983)

Composés ternaires graphite-lithium-tétrahydrofuranne : Synthèse et étude par rayons X et résonance magnétique

Synthetic Metals 7 77-84


Mots-clés

Ingénieur d’études , Protéines de synthèse et chimie bioorthogonale