新型糖苷酶激活的一氧化氮供体：葡萄糖与3-吗啉代亚胺的共轭物

New glycosidase activated nitric oxide donors: glycose and 3-morphorlinosydnonimine conjugates.

作者信息

Cai T Bill, Lu Dongning, Tang Xiaoping, Zhang Yalong, Landerholm Megan, Wang Peng George

机构信息

Department of Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.

出版信息

J Org Chem. 2005 Apr 29;70(9):3518-24. doi: 10.1021/jo050010o.

DOI:10.1021/jo050010o

PMID:15844985

Abstract

[reaction: see text] To achieve site specific delivery of nitric oxide (NO), a new class of glycosidase activated NO donors has been developed. Glucose, galactose, and N-acetylneuraminic acid were covalently coupled to 3-morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a carbamate linkage at the anomeric position. The beta-glycosides were successfully prepared for these conjugates, while the alpha-glycosidic compounds were very unstable. The new stable sugar-NO conjugates could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in biomedical research.

摘要

[反应：见正文] 为了实现一氧化氮（NO）的位点特异性递送，已开发出一类新型的糖苷酶激活的NO供体。葡萄糖、半乳糖和N-乙酰神经氨酸通过异头位置的氨基甲酸酯键与3-吗啉代氧化偶氮烯（SIN-1，一种中离子杂环NO供体）共价偶联。成功制备了这些共轭物的β-糖苷，而α-糖苷化合物非常不稳定。新的稳定糖-NO共轭物在糖苷酶存在下可释放NO。此类NO前药可在生物医学研究中用作酶激活的NO供体。