Sandbox Reserved 817: Difference between revisions

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[[Image:Inhibiteur4.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 ~~its effort elsewhere~~.

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.

One of the discovered compound, 1-(2-(1H-indol-1-yl)ethyl)guanidine showed weak inhibition activity towards BACE1 (about 42% inhibition ratio at the ligand concentration of 100 μM in the fluorescence resonance energy transfer (FRET) assay system). These compound occupied the S1 pocket and the guanidine moiety formed key binding interactions with the two catalytic aspartic acids, <scene name='56/568015/32/1'>Asp32</scene> and <scene name='56/568015/Asp228/1'>Asp228</scene> (Figure 2).

Sandbox Reserved 817: Difference between revisions

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@@ Line 66: / Line 66: @@
 [[Image:Inhibiteur4.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 its effort elsewhere.
+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.
 One of the discovered compound, 1-(2-(1H-indol-1-yl)ethyl)guanidine showed weak inhibition activity towards BACE1 (about 42% inhibition ratio at the ligand concentration of 100 μM in the fluorescence resonance energy transfer (FRET) assay system). These compound occupied the S1 pocket and the guanidine moiety formed key binding interactions with the two catalytic aspartic acids, <scene name='56/568015/32/1'>Asp32</scene> and <scene name='56/568015/Asp228/1'>Asp228</scene> (Figure 2).