N-Hydroxyguanidines as Substrates of Nitric Oxide Synthases

Nitric oxide (NO) has been implicated in a wide variety of disease states. Both inhibitors and substrates of nitric oxide synthase (NOS) could have great therapeutic potential in the treatment of these diseases. There is considerable pharmacological interest in developing inhibitors of NOS, and hundreds of inhibitors have been identified. In contrast, the study on NOS substrates is less active. The advances in the identification, design and development of NOS substrates are discussed in this review. The focus is the chemistry and biochemistry of N-hydroxyguanidines. The crystal structures of substrates bound to NOSs and the mechanisms of NOS catalyzed NO generation from substrates are also discussed.