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1.
PLoS One ; 16(4): e0239791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886551

RESUMO

The European sea bass (Dicentrarchus labrax) exhibits female-biased sexual size dimorphism (SSD) early in development. New tagging techniques provide the opportunity to monitor individual sex-related growth during the post-larval and juvenile stages. We produced an experimental population through artificial fertilization and followed a rearing-temperature protocol (~16°C from hatching to 112 days post-hatching, dph; ~20°C from 117 to 358 dph) targeting a roughly balanced sex ratio. The fish were tagged with microchips between 61 and 96 dph in five tagging trials of 50 fish each; individual standard length (SL) was recorded through repeated biometric measurements performed between 83 to 110 dph via image analyses. Body weight (BW) was modelled using the traits measured on the digital pictures (i.e. area, perimeter and volume). At 117 dph, the fish were tagged with microtags and regularly measured for SL and BW until 335 dph. The experiment ended at 358 dph with the sexing of the fish. The sex-ratio at the end of the experiment was significantly in favor of the females (65.6% vs. 34.4%). The females were significantly longer and heavier than the males from 103 dph (~30 mm SL, ~0.44 g BW) to 165 dph, but the modeling of the growth curves suggests that differences in size already existed at 83 dph. A significant difference in the daily growth coefficient (DGC) was observed only between 96 and 103 dph, suggesting a physiological or biological change occurring during this period. The female-biased SSD pattern in European sea bass is thus strongly influenced by very early growth differences between sexes, as already shown in previous studies, and in any case long before gonadal sex differentiation has been started, and thus probably before sex has been determined. This leads to the hypothesis that early growth might be a cause rather than a consequence of sex differentiation in sea bass.


Assuntos
Bass/crescimento & desenvolvimento , Animais , Bass/fisiologia , Tamanho Corporal , Feminino , Gônadas/crescimento & desenvolvimento , Gônadas/fisiologia , Masculino , Caracteres Sexuais , Diferenciação Sexual , Razão de Masculinidade
2.
Bioorg Med Chem Lett ; 26(10): 2408-2412, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27072910

RESUMO

Introducing a second chiral center on our previously described 1,2,4-triazole, allowed us to increase diversity and elongate the 'C-terminal part' of the molecule. Therefore, we were able to explore mimics of the substance P analogs described as inverse agonists. Some compounds presented affinities in the nanomolar range and potent biological activities, while one exhibited a partial inverse agonist behavior similar to a Substance P analog.


Assuntos
Receptores de Grelina/metabolismo , Triazóis/química , Transferência Ressonante de Energia de Fluorescência , Indóis/química , Indóis/farmacologia , Concentração Inibidora 50 , Ligantes , Receptores de Grelina/agonistas , Relação Estrutura-Atividade , Substância P/química , Triptofano/análogos & derivados , Triptofano/química , Triptofano/farmacologia
3.
Amino Acids ; 45(6): 1395-403, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24142338

RESUMO

Despite correct purity of crude peptides prepared on trityl resin by Fmoc/tBu microwave assisted solid phase peptide synthesis, surprisingly, lower yields than those expected were obtained while preparing C-terminal acid peptides. This could be explained by cyclization/cleavage through diketopiperazine formation during the second amino acid deprotection and third amino acid coupling. However, we provide here evidence that this is not the case and that this yield loss was due to high temperature promoted hydrolysis of the 2-chlorotrityl ester, yielding premature cleavage of the C-terminal acid peptides.


Assuntos
Calefação , Micro-Ondas , Peptídeos/química , Peptídeos/síntese química , Resinas Sintéticas/química , Estrutura Molecular , Peptídeos/isolamento & purificação
4.
Amino Acids ; 44(2): 733-42, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22968665

RESUMO

A large number of bioactive peptides are cyclized through a disulfide bridge. This structural feature is very important for both bioactivity and stability. The oxidation of cysteine side chains is challenging not only to avoid intermolecular reaction leading to oligomers and oxidation of other residues but also to remove solvents and oxidant such as dimethyl sulfoxide. Supported reagents advantageously simplify the work-up of such disulfide bond formation, but may lead to a significant decrease in yield of the oxidized product. In this study, two resins working through different mechanisms were evaluated: Clear-Ox, a supported version of Ellman's reagent and Oxyfold, consisting in a series of oxidized methionine residues. The choice of the supported reagent is discussed on the light of reaction speed, side-products formation and yield considerations.


Assuntos
Cisteína/química , Ácido Ditionitrobenzoico/química , Metionina/química , Safrol/análogos & derivados , Dimetil Sulfóxido/química , Dissulfetos/química , Estrutura Molecular , Oxidantes/química , Oxirredução , Safrol/química
5.
J Comb Chem ; 12(5): 747-53, 2010 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-20715810

RESUMO

The Pipecolic linker is a new highly versatile handle which immobilizes on solid support through a carboxylic acid function a wide range of amines, alcohols, and hydrazines. The anchoring step on pipecolic resin is very easy and efficient, and compounds are released with high purities upon acidic treatment. During this treatment, an oxazolonium intermediate is hydrolyzed, yielding the cleavage of ester or amide bond and the release of free carboxylic acid of the starting linker. In this study, we report the possibility of recycling the pipecolic resin after the use of several trifluoroacetic acid (TFA) cleavage cocktails. We demonstrate that it can be reused up to five times without significant loading decrease.


Assuntos
Técnicas de Química Combinatória , Ácidos Pipecólicos/síntese química , Ciclização , Estrutura Molecular , Ácidos Pipecólicos/química , Estereoisomerismo , Ácido Trifluoracético/química
6.
J Med Chem ; 51(3): 689-93, 2008 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-18193826

RESUMO

Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.


Assuntos
Fármacos Antiobesidade/síntese química , Picolinas/síntese química , Pirazinas/síntese química , Receptores de Grelina/antagonistas & inibidores , Triazóis/síntese química , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Humanos , Células LLC-PK1 , Oligopeptídeos/farmacologia , Picolinas/química , Picolinas/farmacologia , Pirazinas/química , Pirazinas/farmacologia , Ensaio Radioligante , Ratos , Estereoisomerismo , Relação Estrutura-Atividade , Suínos , Triazóis/química , Triazóis/farmacologia
7.
J Comb Chem ; 9(2): 254-62, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17348731

RESUMO

Alpha melanocyte stimulating hormone (alpha-MSH) is a widely distributed hormone. This tridecapeptide exhibits various biological activities mediated through different receptors. alpha-MSH binds to the melanocortin-1 receptor (MC1-R), mainly expressed in keratinocytes and melanocytes, inducing melanogenesis and anti-inflammatory processes. The central His-Phe-Arg-Trp tetrapeptide sequence of alpha-MSH is known to form a turn in the bioactive conformation. To find new potent analogs of alpha-MSH, we decided to introduce non-peptide building blocks in the alpha-MSH sequence. Molecular modeling studies showed that two amino acids of the central core sequence could be replaced by the benzodiazepinone building block without loosing the beta-turn conformation. Benzodiazepines are well-known pharmacophores exhibiting a wide scope of biological activities and are described as constrained dipeptide mimics templates. Although numerous synthetic pathways leading to benzodiazepinones have been described in literature, no methodology has 1,4-benzodiazepine-2,5-diones building blocks bearing a free carboxylic acid function and a protected amino function suitable for incorporation into peptide sequences. In this study, we report the synthesis of peptides with a benzodiazepinone moiety obtained directly during the course of solid-phase peptide synthesis (SPPS). This "on-line" strategy leads to the generation of a 54-member pseudo-peptide library of alpha-MSH analogs. After LC/MS purification, binding assays were performed on the MC1 receptor leading to the discovery of several micromolar ligands.


Assuntos
Benzodiazepinonas/farmacologia , Mimetismo Molecular , Peptídeos/síntese química , Receptor Tipo 1 de Melanocortina/efeitos dos fármacos , Benzodiazepinonas/síntese química , Células Cultivadas , Humanos , Modelos Moleculares
9.
Artigo em Inglês | MEDLINE | ID: mdl-12939491

RESUMO

A series of aminotroponimine and aminotropone derivatives were studied by electrospray mass spectrometry. MS and MS/MS data were acquired according to automated procedures. In the case of mono- and di-halogenated compounds, their specific behavior upon collisionally-activated dissociation conditions provided rapid structural assignments through inexpensive isotopic labeling MS/MS experiments.

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