COPDバイオマーカー診断法の確立を目指したエラスチン架橋アミノ酸類の創製

抄録

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder and is the fourth leading cause of death worldwide. Presently, there is a lack of effective medicines that can prevent progression of the disease, and thus survival rates cannot be improved. The development of biomarkers that can act as indicators of the severity of COPD and the level of patients’ response to therapy would thus aid the drug discovery activities. Elastin fibers are a part of the extracellular matrix and are an essential structural component of the lungs, ligaments, skin, blood vessels, etc. Desmosine (1) and isodesmosine (2) are crosslinking amino acids of elastin. The irreversible degradation of lung elastin that occurs in COPD is known to give rise to these two amino acids, which can be measured in clinical samples by LC-MS. Therefore, 1 and 2 are useful as attractive biomarkers for both drug discovery and rapid diagnosis of COPD. In this study, total synthesis of COPD biomarkers 1 and 2 and the related amino acids are reported utilizing palladium-catalyzed cross-coupling reactions.