The Experts below are selected from a list of 909 Experts worldwide ranked by ideXlab platform
Toyonobu Usuki - One of the best experts on this subject based on the ideXlab platform.
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Preparation of Isodesmosine‐KLH conjugate for ELISA system
Chirality, 2020Co-Authors: Daria A. Baut, Nao Tanaka, Reiko Yokoo, Toyonobu UsukiAbstract:Chronic obstructive pulmonary disease (COPD) is a degenerative condition with limited diagnostic detection efficiency. Currently with no available cure, COPD is associated with irreversible elastic tissue degradation in lungs, which results in release of unusual amino acids, Isodesmosine and desmosine. These biomarkers are potential key elements in enzyme-linked immunosorbent assay (ELISA), an analytical method, which can detect certain compounds including antigens and proteins in easy and affordable manner. In order to target a biomarker with ELISA, it is necessary to prepare its specific antibody, which can be achieved by immunization of host organism with appropriate antigen containing the biomarker. Although preparation of these types of conjugates has been published, desmosine and Isodesmosine used by researchers are obtained from natural sources such as animal tissues. Here, we report the first synthetic preparation of Isodesmosine and keyhole limpet hemocyanin (KLH) conjugate from commercially available chiral amino acids and carrier protein. Formation of the core pyridinium of Isodesmosine was achieved through key reaction-Chichibabin pyridinium synthesis-to deliver a 1,2,3,5-tetrasubstituted pyridinium amino acid selectively. Further modifications involving KLH and maleimide linker provided the target conjugate, which could potentially invoke an immune response to produce anti-Isodesmosine antibody for the ELISA system.
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preparation of Isodesmosine klh conjugate for elisa system
Chirality, 2020Co-Authors: Daria A. Baut, Nao Tanaka, Reiko Yokoo, Toyonobu UsukiAbstract:Chronic obstructive pulmonary disease (COPD) is a degenerative condition with limited diagnostic detection efficiency. Currently with no available cure, COPD is associated with irreversible elastic tissue degradation in lungs, which results in release of unusual amino acids, Isodesmosine and desmosine. These biomarkers are potential key elements in enzyme-linked immunosorbent assay (ELISA), an analytical method, which can detect certain compounds including antigens and proteins in easy and affordable manner. In order to target a biomarker with ELISA, it is necessary to prepare its specific antibody, which can be achieved by immunization of host organism with appropriate antigen containing the biomarker. Although preparation of these types of conjugates has been published, desmosine and Isodesmosine used by researchers are obtained from natural sources such as animal tissues. Here, we report the first synthetic preparation of Isodesmosine and keyhole limpet hemocyanin (KLH) conjugate from commercially available chiral amino acids and carrier protein. Formation of the core pyridinium of Isodesmosine was achieved through key reaction-Chichibabin pyridinium synthesis-to deliver a 1,2,3,5-tetrasubstituted pyridinium amino acid selectively. Further modifications involving KLH and maleimide linker provided the target conjugate, which could potentially invoke an immune response to produce anti-Isodesmosine antibody for the ELISA system.
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Preparation of Protected 13Cn-Labeled Isodesmosines: Mechanistic Insight of Isodesmosine Formation:
Natural Product Communications, 2019Co-Authors: Nao Tanaka, Toyonobu UsukiAbstract:Isodesmosine is a pyridinium amino acid that contributes to elastin’s crosslinking structure. It is known to form by condensation and aromatization of 3 allysines and 1 lysine, preceded by previous...
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total synthesis of Isodesmosine by stepwise regioselective negishi and sonogashira cross coupling reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Yong Y Lin, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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Total Synthesis of Isodesmosine by Stepwise, Regioselective Negishi and Sonogashira Cross‐Coupling Reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
Yohei Koseki - One of the best experts on this subject based on the ideXlab platform.
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total synthesis of Isodesmosine by stepwise regioselective negishi and sonogashira cross coupling reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Yong Y Lin, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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Total Synthesis of Isodesmosine by Stepwise, Regioselective Negishi and Sonogashira Cross‐Coupling Reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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pr otf 3 promoted chichibabin pyridine synthesis of Isodesmosine in h2o meoh
Tetrahedron Letters, 2014Co-Authors: Takanori Sugimura, Yohei Koseki, Akira Komatsu, Toyonobu UsukiAbstract:Abstract 1,2,3,5-Tetrasubstituted pyridinium amino acid Isodesmosine is a crosslinking amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we report an application of the Chichibabin pyridine synthesis to the total synthesis of Isodesmosine. Specifically, the appropriate protected lysine and the corresponding aldehyde were reacted using Pr(OTf) 3 in H 2 O/MeOH.
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Biomimetic Chichibabin Pyridine Synthesis of the COPD Biomarkers and Elastin Cross-Linkers Isodesmosine and Desmosine
Organic letters, 2014Co-Authors: Toyonobu Usuki, Takanori Sugimura, Akira Komatsu, Yohei KosekiAbstract:The tetrasubstituted pyridinium amino acids Isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of Isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported.
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Biomimetic Chichibabin Pyridine Synthesis of the COPD Biomarkers and Elastin Cross-Linkers Isodesmosine and Desmosine
2014Co-Authors: Toyonobu Usuki, Takanori Sugimura, Akira Komatsu, Yohei KosekiAbstract:The tetrasubstituted pyridinium amino acids Isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of Isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported
Yong Y Lin - One of the best experts on this subject based on the ideXlab platform.
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Biomarkers in Alpha-1 Antitrypsin Deficiency Chronic Obstructive Pulmonary Disease.
Annals of the American Thoracic Society, 2016Co-Authors: Gerard M Turino, Jerome O. Cantor, Yong Y LinAbstract:Biomarkers of pathogenesis in chronic obstructive pulmonary disease (COPD) can significantly accelerate drug development. In COPD related to alpha-1 antitrypsin deficiency, the role of neutrophil elastase and its inhibition by alpha-1 antitrypsin protein focused interest on elastin degradation and the development of pulmonary emphysema. Amino acids desmosine and Isodesmosine are unique cross-links in mature elastin fibers and can serve as biomarkers of elastin degradation when measured in body fluids. This review gives a perspective on what has been learned by the earliest measurements of desmosine and Isodesmosine followed by later studies using methods of increased sensitivity and specificity and the meaning for developing new therapies. Also included are brief statements on the biomarkers fibrinogen, CC-16, and Aa-Val-360 in COPD.
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total synthesis of Isodesmosine by stepwise regioselective negishi and sonogashira cross coupling reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Yong Y Lin, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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Stable deuterium internal standard for the isotope-dilution LC–MS/MS analysis of elastin degradation
Analytical biochemistry, 2013Co-Authors: Gerard M Turino, Toyonobu Usuki, Takahiro Hayashi, Hiroto Yanuma, Yong Y LinAbstract:Abstract Chemical synthesis of the deuterium isotope desmosine-d 4 has been achieved. This isotopic compound possesses all four deuterium atoms at the alkanyl carbons of the alkyl amino acid substitution in the desmosine molecule and is stable toward acid hydrolysis; this is required in the measurement of two crosslinking molecules, desmosine and Isodesmosine, as biomarkers of elastic tissue degradation. The degradation of elastin occurs in several widely prevalent diseases. The synthesized desmosine-d 4 is used as the internal standard to develop an accurate and sensitive isotope-dilution liquid chromatography–tandem mass spectrometry analysis, which can serve as a generalized method for an accurate analysis of desmosine and Isodesmosine as biomarkers in many types of biological tissues involving elastin degradation.
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Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease.
American journal of respiratory and critical care medicine, 2011Co-Authors: Gerard M Turino, Jerome O. Cantor, Yong Y Lin, Maurizio LuisettiAbstract:Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and is now the third leading cause of death in the United States. There is a lack of therapies that can stop progression of the disease and improve survival. New drug discovery can be aided by the development of biomarkers, which can act as indicators of severity in the course of the disease and responses to therapy. This perspective brings together the laboratory and clinical evidence, which suggest that elastin degradation products can fulfill the need for such a biomarker. Elastin is a recognized target for injury in COPD. The amino acids desmosine and Isodesmosine exist only in matrix elastin; can be measured specifically and sensitively in plasma, urine, and sputum; and indicate changes in the systemic balance between elastase activity and elastase inhibition brought on by the systemic inflammatory state. The biomarker levels in sputum reflect the state of elastin degradation in the lung specifically. Clinical data accumulated over several decades indicate correlations of desmosine and Isodesmosine levels with COPD of varying severity and responses to therapy.
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The effect of tiotropium therapy on markers of elastin degradation in COPD
Respiratory research, 2009Co-Authors: Yong Y Lin, Lori Tartell, Gerard M TurinoAbstract:Background Desmosine and Isodesmosine (D/I) are cross-linking amino acids which are present only in mature elastin. Changes in their concentration in body fluids indicate changes in elastin degradation and can be a reflection of tissue elastase activity. This study was undertaken to determine whether continuous therapy with the long-acting bronchodilator Tiotropium bromide (TTP) could result in reductions in D/I as measured by mass spectrometry in plasma, urine and sputum.
Takanori Sugimura - One of the best experts on this subject based on the ideXlab platform.
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total synthesis of Isodesmosine by stepwise regioselective negishi and sonogashira cross coupling reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Yong Y Lin, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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Total Synthesis of Isodesmosine by Stepwise, Regioselective Negishi and Sonogashira Cross‐Coupling Reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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pr otf 3 promoted chichibabin pyridine synthesis of Isodesmosine in h2o meoh
Tetrahedron Letters, 2014Co-Authors: Takanori Sugimura, Yohei Koseki, Akira Komatsu, Toyonobu UsukiAbstract:Abstract 1,2,3,5-Tetrasubstituted pyridinium amino acid Isodesmosine is a crosslinking amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we report an application of the Chichibabin pyridine synthesis to the total synthesis of Isodesmosine. Specifically, the appropriate protected lysine and the corresponding aldehyde were reacted using Pr(OTf) 3 in H 2 O/MeOH.
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Biomimetic Chichibabin Pyridine Synthesis of the COPD Biomarkers and Elastin Cross-Linkers Isodesmosine and Desmosine
Organic letters, 2014Co-Authors: Toyonobu Usuki, Takanori Sugimura, Akira Komatsu, Yohei KosekiAbstract:The tetrasubstituted pyridinium amino acids Isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of Isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported.
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Biomimetic Chichibabin Pyridine Synthesis of the COPD Biomarkers and Elastin Cross-Linkers Isodesmosine and Desmosine
2014Co-Authors: Toyonobu Usuki, Takanori Sugimura, Akira Komatsu, Yohei KosekiAbstract:The tetrasubstituted pyridinium amino acids Isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of Isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported
Keita Ogawa - One of the best experts on this subject based on the ideXlab platform.
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total synthesis of Isodesmosine by stepwise regioselective negishi and sonogashira cross coupling reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Yong Y Lin, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
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Total Synthesis of Isodesmosine by Stepwise, Regioselective Negishi and Sonogashira Cross‐Coupling Reactions
European Journal of Organic Chemistry, 2015Co-Authors: Yohei Koseki, Takanori Sugimura, Keita Ogawa, Rina Suzuki, Haruka Yamada, Yoshiro Masuyama, Noriyuki Suzuki, Toyonobu UsukiAbstract:Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of Isodesmosine. The key features of this synthesis are stepwise and regioselective palladium-catalyzed Negishi and Sonogashira cross-coupling reactions for efficient introduction of amino acid segments on the pyridine ring.
