2iwx: Difference between revisions

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==Overview==

A series of benzo-macrolactones of varying ring size and conformation has, been prepared by chemical synthesis and evaluated by structural and, biological techniques. Thus, 12- to 16-membered lactones were obtained by, concise routes, involving ring-closing metathesis as a key step. In enzyme, assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the, ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and, 15-membered lactones with the N-terminal domain of yeast Hsp90, showing, that they bind similarly to the "natural" 14-membered radicicol. The most, active compounds in the ATPase assays also showed the greatest, growth-inhibitory potency in HCT116 human colon cancer cells and the, established molecular signature of Hsp90 inhibition, i.e., depletion of, client proteins with upregulation of Hsp70.

A series of benzo-macrolactones of varying ring size and conformation has been prepared by chemical synthesis and evaluated by structural and biological techniques. Thus, 12- to 16-membered lactones were obtained by concise routes, involving ring-closing metathesis as a key step. In enzyme assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and 15-membered lactones with the N-terminal domain of yeast Hsp90, showing that they bind similarly to the "natural" 14-membered radicicol. The most active compounds in the ATPase assays also showed the greatest growth-inhibitory potency in HCT116 human colon cancer cells and the established molecular signature of Hsp90 inhibition, i.e., depletion of client proteins with upregulation of Hsp70.

==About this Structure==

Line 13:

[[Category: Saccharomyces cerevisiae]]

[[Category: Single protein]]

[[Category: Pearl, L.H.]]

[[Category: Pearl, L H.]]

[[Category: Prodromou, C.]]

[[Category: Roe, S.M.]]

[[Category: Roe, S M.]]

[[Category: M1S]]

[[Category: atp-binding]]

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[[Category: nucleotide-binding]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-A series of benzo-macrolactones of varying ring size and conformation has, been prepared by chemical synthesis and evaluated by structural and, biological techniques. Thus, 12- to 16-membered lactones were obtained by, concise routes, involving ring-closing metathesis as a key step. In enzyme, assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the, ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and, 15-membered lactones with the N-terminal domain of yeast Hsp90, showing, that they bind similarly to the "natural" 14-membered radicicol. The most, active compounds in the ATPase assays also showed the greatest, growth-inhibitory potency in HCT116 human colon cancer cells and the, established molecular signature of Hsp90 inhibition, i.e., depletion of, client proteins with upregulation of Hsp70.
+A series of benzo-macrolactones of varying ring size and conformation has been prepared by chemical synthesis and evaluated by structural and biological techniques. Thus, 12- to 16-membered lactones were obtained by concise routes, involving ring-closing metathesis as a key step. In enzyme assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and 15-membered lactones with the N-terminal domain of yeast Hsp90, showing that they bind similarly to the "natural" 14-membered radicicol. The most active compounds in the ATPase assays also showed the greatest growth-inhibitory potency in HCT116 human colon cancer cells and the established molecular signature of Hsp90 inhibition, i.e., depletion of client proteins with upregulation of Hsp70.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Pearl, L.H.]]
+[[Category: Pearl, L H.]]
 [[Category: Prodromou, C.]]
-[[Category: Roe, S.M.]]
+[[Category: Roe, S M.]]
 [[Category: M1S]]
 [[Category: atp-binding]]
@@ Line 26: / Line 26: @@
 [[Category: nucleotide-binding]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:39:08 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:56:52 2008''