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Discovery and structural analyses of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs.

Abstract：

:Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 ± 3, 5.0 ± 2.0, and 8.5 ± 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Nakao A,Suzuki H,Ueno H,Iwasaki H,Setsuta T,Kashima A,Sunada S

doi

10.1016/j.bmc.2015.05.018

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

4952-4969

issue

15

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)00418-6

journal_volume

23

pub_type

杂志文章

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