RESUMO
Desmosine-CH2, an analog of the elastic tissue degradation biomarker desmosine, can be regarded as a potential internal standard for precise quantification of desmosines by LC-MS/MS. In this study, the chemical synthesis of desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of desmosine-CH2 was also achieved.
Assuntos
Desmosina/análise , Elastina/química , Biomarcadores/análise , Cromatografia Líquida , Desmosina/síntese química , Conformação Molecular , Espectrometria de Massas em TandemRESUMO
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.
Assuntos
Desmosina/síntese química , Elastina/metabolismo , Isodesmosina/síntese química , Doença Pulmonar Obstrutiva Crônica/metabolismo , Compostos de Piridínio/síntese química , Biomarcadores/metabolismo , Biomimética , Reagentes de Ligações Cruzadas/química , Desmosina/química , Desmosina/farmacologia , Elastina/química , Humanos , Isodesmosina/química , Isodesmosina/farmacologia , Elementos da Série dos Lantanídeos/química , Estrutura Molecular , Piridinas/metabolismo , Compostos de Piridínio/química , Compostos de Piridínio/farmacologiaRESUMO
Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total synthesis of (+)-desmosine was achieved in 11% overall yield in 13 steps utilizing stepwise and regioselective Sonogashira cross-coupling reactions.
Assuntos
Reagentes de Ligações Cruzadas/síntese química , Desmosina/síntese química , Elastina/química , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Biomarcadores/química , Reagentes de Ligações Cruzadas/química , Desmosina/química , Estrutura Molecular , EstereoisomerismoRESUMO
Progressive crosslinking of proteins appears to be a general phenomenon in aging cells and tissues. Crosslinked proteins can form insoluble aggregates which become increasingly resistant to proteolysis as more crosslinks form. However, most evidence for progressive crosslinking with age is indirect, and little is known about the chemical mechanisms involved. We have therefore developed a method for detection and isolation of any type of stable covalent crosslink from protein hydrolysates which requires no prior knowledge of the molecular structure of whatever crosslink(s) may be present. It utilizes the specificity of the diphenylborinic acid reagent for alpha-amino acid groups and the chromatographic properties and uv absorbance of the crosslink derivatives. The method is demonstrated using eight different crosslinks from collagen and fibrin, and a general procedure is given for detection of any type of crosslink in a protein hydrolysate.
