論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Synthesis of radioiodinated probes targeted toward matrix metalloproteinase-12
掲載誌名	正式名：Bioorganic and Medicinal Chemistry Letters ISSNコード：1464-3405
出版社	Elsevier Ltd
巻・号・頁	28(2),pp.193-195
著者・共著者	Masayori Hagimori,Takashi Temma,Shinji Kudo,Kohei Sano,Naoya Kondo,Takahiro Mukai
発行年月	2018/01/15
概要	Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP family that is responsible for the degradation of extracellular matrix, and is associated with the inflammatory process of chronic obstructive pulmonary disease (COPD). COPD, characterized by progressive and irreversible airflow obstruction, is recently a major cause of mortality and morbidity worldwide. Herein, to develop radioiodinated probes for the early diagnosis of COPD, we designed and synthesized novel MMP-12-targeted dibenzofuran compounds (1–3) with a variety of linker structures (carbamate, amide, and sulfonamide). In competitive enzyme activity assays, it was revealed that the linker structures significantly affected the inhibitory activity against and selectivity for MMP-12. Compound 1, with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC50 = 8.5 nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide linker. Using bromo-substituted carbamate 13 as a radioiodination precursor, [125I]1 was successfully prepared to high radiochemical purity (over 98%) and good specific radioactivity (4.1 GBq/μmol). These results suggest that radioiodinated compound 1 is potent as a novel MMP-12-targeted probe.
DOI	10.1016/j.bmcl.2017.11.027
PMID	29191557