2rcx: Difference between revisions

Line 4:

==Overview==

Boronic acids have proved to be promising selective inhibitors of, beta-lactamases, acting as transition state analogues. Starting from a, previously described nanomolar inhibitor of AmpC beta-lactamase, three new, inhibitors were designed to gain interactions with highly conserved, residues, such as Asn343, and to bind more tightly to the enzyme. Among, these, one was obtained by stereoselective synthesis and succeeded in, placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC., Nevertheless, it failed at improving affinity, when compared to the lead, from which it was derived. The origins of this structural and energetic, discrepancy are discussed.

Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.

==About this Structure==

Line 17:

[[Category: Morandi, S.]]

[[Category: Prati, F.]]

[[Category: Shoichet, B.K.]]

[[Category: Shoichet, B K.]]

[[Category: PO4]]

[[Category: SM4]]

Line 27:

[[Category: serine hydrolase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 11~~:59:46 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:15 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-Boronic acids have proved to be promising selective inhibitors of, beta-lactamases, acting as transition state analogues. Starting from a, previously described nanomolar inhibitor of AmpC beta-lactamase, three new, inhibitors were designed to gain interactions with highly conserved, residues, such as Asn343, and to bind more tightly to the enzyme. Among, these, one was obtained by stereoselective synthesis and succeeded in, placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC., Nevertheless, it failed at improving affinity, when compared to the lead, from which it was derived. The origins of this structural and energetic, discrepancy are discussed.
+Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.
 ==About this Structure==
@@ Line 17: / Line 17: @@
 [[Category: Morandi, S.]]
 [[Category: Prati, F.]]
-[[Category: Shoichet, B.K.]]
+[[Category: Shoichet, B K.]]
 [[Category: PO4]]
 [[Category: SM4]]
@@ Line 27: / Line 27: @@
 [[Category: serine hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:59:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:46:15 2008''