Sandbox Reserved 817: Difference between revisions
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<ref name="first">PMID:18005427</ref> | <ref name="first">PMID:18005427</ref> | ||
__NOTOC__ | __NOTOC__ | ||
=== Post translational modification === | === Post translational modification === | ||
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BACE1 may also be involved in other functions in the brain like the regulation of neuronal function, axonal growth, neuroprotection or synapse formation. It could ever have a role in the immunity system as several of its substrates are molecules of the immune system (like IL-1R2). These cross functions need to be investigated before any inhibitor is put to the market. | BACE1 may also be involved in other functions in the brain like the regulation of neuronal function, axonal growth, neuroprotection or synapse formation. It could ever have a role in the immunity system as several of its substrates are molecules of the immune system (like IL-1R2). These cross functions need to be investigated before any inhibitor is put to the market. | ||
<Structure load='4ivs' size='400' frame='true' align='right' caption='Amino acid sequence of Beta secretase 1' scene='Insert optional scene name here' /> | |||
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[[Image: | [[Image:Inhibitor.jpg|right|300px|thumb|'''Figure 2 :''' Docking study on compound 4 bound to BACE1. The coordinates of BACE1 was taken from the crystal structure of 1FKN. The protein is shown in cartoon, while the important residues and ligand 4 are shown in stick model.'']] | ||
In the past, major efforts in designing BACE1 inhibitors were focused on the transition state analogs such as hydroxyethylamines, hydroxyethylene, and tatine-based peptidomimetic inhibitors but their relatively large sizes and excessive number of hydrogen-bond donors and acceptors made it difficult for them to penetrate the blood brain barrier. Therefore the scientific community focused on other coompounds. | In the past, major efforts in designing BACE1 inhibitors were focused on the transition state analogs such as hydroxyethylamines, hydroxyethylene, and tatine-based peptidomimetic inhibitors but their relatively large sizes and excessive number of hydrogen-bond donors and acceptors made it difficult for them to penetrate the blood brain barrier. Therefore the scientific community focused on other coompounds. | ||
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Analogs were also synthesized based on indole. The indole group pointed toward the back of the S1’ pocket forming a cation-πinteraction with <scene name='56/568015/Arg235/1'>Arg235</scene>, which appears to contribute further interactions to improve the potency of the inhibitor. <ref name="three">PMID:23681056</ref> | Analogs were also synthesized based on indole. The indole group pointed toward the back of the S1’ pocket forming a cation-πinteraction with <scene name='56/568015/Arg235/1'>Arg235</scene>, which appears to contribute further interactions to improve the potency of the inhibitor. <ref name="three">PMID:23681056</ref> | ||