Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase

Rossiter, S., Smith, C. L., Malaki, M., Nandi, M., Gill, H., Leiper, J. M. , Vallance, P. and Selwood, D. L. (2005) Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase. Journal of Medicinal Chemistry, 48(14), pp. 4670-4678. (doi:10.1021/jm050187a) (PMID:16000003)

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Abstract

The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leiper, Professor James
Authors: Rossiter, S., Smith, C. L., Malaki, M., Nandi, M., Gill, H., Leiper, J. M., Vallance, P., and Selwood, D. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Medicinal Chemistry
Publisher:American Chemical Society
ISSN:0022-2623
ISSN (Online):1520-4804
Published Online:14 January 2005

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