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        Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase

        Author
        Rossiter, S.
        Smith, C.L.
        Malaki, M.
        Nandi, M.
        Gill, H.
        Leiper, J.M.
        Vallance, P.
        Selwood, D.L.
        Attention
        2299/2619
        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.
        Publication date
        2005
        Published in
        Journal of Medicinal Chemistry
        Published version
        https://doi.org/10.1021/jm050187a
        Other links
        http://hdl.handle.net/2299/2619
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