2ces: Difference between revisions

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==Overview==

Inhibition of glycosidases has great potential in the quest for highly, potent and specific drugs to treat diseases such as diabetes, cancer, and, viral infections. One of the most effective ways of designing such, compounds is by mimicking the transition state. Here we describe the, structural, kinetic, and thermodynamic dissection of binding of two, glucoimidazole-derived compounds, which are among the most potent, glycosidase inhibitors reported to date, with two family 1, beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety, improves binding by a factor of 20-80-fold, this does not appear to result, from better noncovalent interactions with the enzyme; instead, improved, affinity may be derived from significantly better entropic contributions, to binding displayed by the phenethyl-substituted imidazole compound.

Inhibition of glycosidases has great potential in the quest for highly potent and specific drugs to treat diseases such as diabetes, cancer, and viral infections. One of the most effective ways of designing such compounds is by mimicking the transition state. Here we describe the structural, kinetic, and thermodynamic dissection of binding of two glucoimidazole-derived compounds, which are among the most potent glycosidase inhibitors reported to date, with two family 1 beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety improves binding by a factor of 20-80-fold, this does not appear to result from better noncovalent interactions with the enzyme; instead, improved affinity may be derived from significantly better entropic contributions to binding displayed by the phenethyl-substituted imidazole compound.

==About this Structure==

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[[Category: Single protein]]

[[Category: Thermotoga maritima]]

[[Category: Davies, G.J.]]

[[Category: Davies, G J.]]

[[Category: Gloster, T.M.]]

[[Category: Gloster, T M.]]

[[Category: Roberts, S.]]

[[Category: Vasella, A.]]

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[[Category: transition state mimic]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:47:52 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Inhibition of glycosidases has great potential in the quest for highly, potent and specific drugs to treat diseases such as diabetes, cancer, and, viral infections. One of the most effective ways of designing such, compounds is by mimicking the transition state. Here we describe the, structural, kinetic, and thermodynamic dissection of binding of two, glucoimidazole-derived compounds, which are among the most potent, glycosidase inhibitors reported to date, with two family 1, beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety, improves binding by a factor of 20-80-fold, this does not appear to result, from better noncovalent interactions with the enzyme; instead, improved, affinity may be derived from significantly better entropic contributions, to binding displayed by the phenethyl-substituted imidazole compound.
+Inhibition of glycosidases has great potential in the quest for highly potent and specific drugs to treat diseases such as diabetes, cancer, and viral infections. One of the most effective ways of designing such compounds is by mimicking the transition state. Here we describe the structural, kinetic, and thermodynamic dissection of binding of two glucoimidazole-derived compounds, which are among the most potent glycosidase inhibitors reported to date, with two family 1 beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety improves binding by a factor of 20-80-fold, this does not appear to result from better noncovalent interactions with the enzyme; instead, improved affinity may be derived from significantly better entropic contributions to binding displayed by the phenethyl-substituted imidazole compound.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Thermotoga maritima]]
-[[Category: Davies, G.J.]]
+[[Category: Davies, G J.]]
-[[Category: Gloster, T.M.]]
+[[Category: Gloster, T M.]]
 [[Category: Roberts, S.]]
 [[Category: Vasella, A.]]
@@ Line 28: / Line 28: @@
 [[Category: transition state mimic]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:34:29 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:47:52 2008''