The Experts below are selected from a list of 1191 Experts worldwide ranked by ideXlab platform
Shinya Oishi - One of the best experts on this subject based on the ideXlab platform.
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Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
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structure activity relationship study on senktide for development of novel potent neurokinin 3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
Ryosuke Misu - One of the best experts on this subject based on the ideXlab platform.
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Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
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structure activity relationship study on senktide for development of novel potent neurokinin 3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
Jan V. Nørgaard - One of the best experts on this subject based on the ideXlab platform.
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Nontargeted LC–MS metabolomics approach for metabolic profiling of plasma and urine from pigs fed branched chain amino Acids for maximum growth performance
Journal of Proteome Research, 2016Co-Authors: Elham A. Soumeh, Mette S. Hedemann, Hanne D. Poulsen, Etienne Corrent, Jacob Van Milgen, Jan V. NørgaardAbstract:The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino Acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to the animal growth performance. Three dose–response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a nontargeted LC–MS approach to characterize the metabolic profile of biofluids when dietary BCAAs are optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic Acid, tauroursodeoxycholic Acid, and taurocholic Acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric Acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic Acid and choline and relatively decreased excretion of 2-Aminoadipic Acid, acetyl-dl-valine, Ile, 2-methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic Acid and taurocholic Acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-Aminoadipic Acid and elevated urinary excretion of ascorbic Acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA.
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Nontargeted LC–MS Metabolomics Approach for Metabolic Profiling of Plasma and Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance
2016Co-Authors: Elham A. Soumeh, Mette S. Hedemann, Etienne Corrent, Jacob Van Milgen, Hanne D. Poulsen, Jan V. NørgaardAbstract:The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino Acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to the animal growth performance. Three dose–response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a nontargeted LC–MS approach to characterize the metabolic profile of biofluids when dietary BCAAs are optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic Acid, tauroursodeoxycholic Acid, and taurocholic Acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric Acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic Acid and choline and relatively decreased excretion of 2-Aminoadipic Acid, acetyl-dl-valine, Ile, 2-methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic Acid and taurocholic Acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-Aminoadipic Acid and elevated urinary excretion of ascorbic Acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA
Vincent M Monnier - One of the best experts on this subject based on the ideXlab platform.
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mechanism of lysine oxidation in human lens crystallins during aging and in diabetes
Journal of Biological Chemistry, 2009Co-Authors: Xingjun Fan, Christopher Strauch, Jianye Zhang, Mathilde Theves, Ina Nemet, X Liu, Juan Qian, Frank J Giblin, Vincent M MonnierAbstract:Abstract Oxidative mechanisms during nuclear sclerosis of the lens are poorly understood, in particular metal-catalyzed oxidation. The lysyl oxidation product adipic semialdehyde (allysine, ALL) and its oxidized end-product 2-Aminoadipic Acid (2-AAA) were determined as a function of age and presence of diabetes. Surprisingly, whereas both ALL and 2-AAA increased with age and strongly correlated with cataract grade and protein absorbance at 350 nm, only ALL formation but not 2-AAA was increased by diabetes. To clarify the mechanism of oxidation, rabbit lenses were treated with hyperbaric oxygen (HBO) for 48 h, and proteins were analyzed by gas and liquid chromatography mass spectrometry for ALL, 2-AAA, and multiple glycation products. Upon exposure to HBO, rabbit lenses were swollen, and nuclei were yellow. Protein-bound ALL increased 8-fold in the nuclear protein fractions versus controls. A dramatic increase in methyl-glyoxal hydroimidazolone and carboxyethyl-lysine but no increase of 2-AAA occurred, suggesting more drastic conditions are needed to oxidize ALL into 2-AAA. Indeed the latter formed only upon depletion of glutathione and was catalyzed by H2O2. Neither carboxymethyl-lysine nor glyoxal hydroimidazolone, two markers of glyco-/lipoxidation, nor markers of lenticular glycemia (fructose-lysine, glucospane) were elevated by HBO, excluding significant lipid peroxidation and glucose involvement. The findings strongly implicate dicarbonyl/metal catalyzed oxidation of lysine to allysine, whereby low GSH combined with ascorbate-derived H2O2 likely contributes toward 2-AAA formation, since virtually no 2-AAA formed in the presence of methylglyoxal instead of ascorbate. An important translational conclusion is that chelating agents might help delay nuclear sclerosis.
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aging diabetes and renal failure catalyze the oxidation of lysyl residues to 2 Aminoadipic Acid in human skin collagen
Annals of the New York Academy of Sciences, 2008Co-Authors: David R Sell, Christopher Strauch, Wei Shen, Vincent M MonnierAbstract:The epsilon-amino group of lysyl residues oxidatively deaminates in the presence of alpha-dicarbonyl sugars and redox-active metals forming alpha-Aminoadipic Acid-delta-semialdehyde (allysine; Suyama's hypothesis), which can further oxidize into 2-Aminoadipic Acid. Here we show that 2-Aminoadipic Acid is significantly (P 2 nmol/mg collagen).
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2 Aminoadipic Acid is a marker of protein carbonyl oxidation in the aging human skin effects of diabetes renal failure and sepsis
Biochemical Journal, 2007Co-Authors: David R Sell, Christopher Strauch, Wei Shen, Vincent M MonnierAbstract:We hypothesized that the epsilon-amino group of lysine residues in longlived proteins oxidatively deaminates with age forming the carbonyl compound, allysine (alpha-Aminoadipic Acid-delta-semialdehyde), which can further oxidize into 2-Aminoadipic Acid. In the present study, we measured both products in insoluble human skin collagen from n=117 individuals of age range 10-90 years, of which n=61 and n=56 were non-diabetic and diabetic respectively, and a total of n=61 individuals had either acute or chronic renal failure. Allysine was reduced by borohydride into 6-hydroxynorleucine and both products were measured in Acid hydrolysates by selective ion monitoring gas chromatography (GC)-MS. The results showed that 2-Aminoadipic Acid (P<0.0001), but not 6-hydroxynorleucine (P=0.14), significantly increased with age reaching levels of 1 and 0.3 mmol/mol lysine at late age respectively. Diabetes in the absence of renal failure significantly (P<0.0001) increased 2-Aminoadipic Acid up to <3 mmol/mol, but not 6-hydroxynorleucine (levels<0.4 mmol/mol, P=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to <0.5 and 8 mmol/mol for 6-hydroxynorleucine and 2-Aminoadipic Acid respectively. Septicaemia significantly (P<0.0001) elevated 2-Aminoadipic Acid in non-diabetic, but not diabetic individuals, and mildly correlated with other glycoxidation markers, carboxymethyl-lysine and the methylglyoxal-derived products, carboxyethyl-lysine, argpyrimidine and MODIC (methylglyoxal-derived imidazolium cross-link). These results provide support for the presence of metal-catalysed oxidation (the Suyama pathway) in diabetes and the possible activation of myeloperoxidase during sepsis. We conclude that 2-Aminoadipic Acid is a more reliable marker for protein oxidation than its precursor, allysine. Its mechanism of formation in each of these conditions needs to be elucidated.
Satoshi Ohkura - One of the best experts on this subject based on the ideXlab platform.
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Structure–activity relationship study on senktide for development of novel potent neurokinin-3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
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structure activity relationship study on senktide for development of novel potent neurokinin 3 receptor selective agonists
MedChemComm, 2015Co-Authors: Ryosuke Misu, Taro Noguchi, Hiroaki Ohno, Ai Yamada, Takashi Yamamura, Fuko Matsuda, Koki Yamamoto, Hiroaki Okamura, Satoshi Ohkura, Shinya OishiAbstract:Neurokinin B (NKB) regulates the secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus via activation of the cognate neurokinin-3 receptor (NK3R). The stimulatory effect of NKB and the derivatives on gonadotropin secretion can potentially be used for development of novel regulatory and therapeutic agents for reproductive dysfunctions. Here, we report a comprehensive structure–activity relationship study on the NK3R-selective agonist peptide, senktide. Substitution of the N-terminal succinyl-Asp substructure in senktide with oxalyl-Glu, oxalyl-D-Glu or oxalyl-L-2-Aminoadipic Acid (Aad) increased receptor binding and NK3R activation. Among these modifications, the oxalyl-D-Glu substructure prevented neutral endopeptidase (NEP) 24.11-mediated degradation, thus providing a novel NK3R agonist peptide with favourable biological and stability properties.
