Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase
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.
Rossiter, Sharon,Smith, Caroline L.,Malaki, Mohammed,Nandi, Manasi,Gill, Herpreet,Leiper, James M.,Vallance, Patrick,Selwood, David L.
Effects of arginine homologues and other guanidino compounds on the ATP level and glucose oxidation in isolated fat cells
The arginine homologues 2 amino 3 guanidinopropionic acid, 2 amino 4 guanidinobutyric acid and 2 amino 6 guanidinocaproic acid (= homoarginine) were synthesized and transformed into their methyl esters. The latter, together with arginine methyl ester, arg
Schwegler,Stock
p. 839 - 844
(2007/10/05)
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