Proteinic AChE inhibitors

The natural toxins onchidal and fasciculins behave as anti-ChE agents. Onchidal is an active site-directed irreversible inhibitor of AChE, and fasciculins are proteinic AChE inhibitors which bind to a peripheral regulatory anionic site of AChE in a noncompetitive and irreversible manner. 

A large number of organic compounds reversible or irreversibly inhibits AChE (Long, 1963), which bind either to the esteratic or the anionic subsite of AChE catalytic site or to the peripheral site of the enzymes. Most of them are S5mthetic substances, sometimes with insecticidal properties. Few natural inhibitors of AChE are known and, to date, fasciculins are the only known proteinic AChE inhibitors. They have been shown to display a powerful inhibitory activity toward mammalian AChE. lodination of Fas3 provided a fully active and specific probe of fasciculin-binding sites on rat brain AChE (Marchot et al., 1993). These authors demonstrate that fasciculins bind on a peripheral site of AChE, distinct from the catalytic site and, at least partly, common with the sites on which some cationic inhibitors and the substrate in excess bind since phosphorylation of the catalytic serine (esteratic subsite) by [l,3- H]diisopro-pyl fluorophosphate can still occur on the Fas3. In the... 

A large number of organic compounds reversibly or irreversibly inhibit AChE (Long, 1963), which bind either to the esteratic or the anionic subsite of AChE catalytic site or to the peripheral site of the enzyme. Most of them are synthetic substances, sometimes bearing insecticidal properties. Few natural inhibitors of AChE are known and, to date, fasciculins are the only known proteinic AChE... 

The examples from literature and the hrst application of PSSC clustering in the discovery of inhibitors for proteins from the Cdc25A, AChE and 1 lfdTDSi/2 cluster convincingly demonstrates that application of target clustering based on protein structure similarity in conjunction with natural... 

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