Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase

2003 ◽  
Vol 1 (12) ◽  
pp. 2075-2083 ◽  
Author(s):  
Miguel D. Toscano ◽  
Martyn Frederickson ◽  
David P. Evans ◽  
John R. Coggins ◽  
Chris Abell ◽  
...  
Keyword(s):  
Type Ii ◽  
Design Synthesis ◽  
Type Ii Dehydroquinase

Rational Design, Synthesis, and Evaluation of Nanomolar Type II Dehydroquinase Inhibitors

ChemMedChem ◽  
2007 ◽  
Vol 2 (7) ◽  
pp. 1015-1029 ◽  
Author(s):  
Richard J. Payne ◽  
Fabienne Peyrot ◽  
Olivier Kerbarh ◽  
Andrew D. Abell ◽  
Chris Abell
Keyword(s):  
Rational Design ◽  
Type Ii ◽  
Design Synthesis ◽  
Type Ii Dehydroquinase

scholarly journals Design, Synthesis and Biological Evaluation of N4-Sulfonamido-Succinamic, Phthalamic, Acrylic and Benzoyl Acetic Acid Derivatives as Potential DPP IV Inhibitors

2013 ◽  
Vol 7 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Reema Abu Khalaf ◽  
Ghassan Abu Sheikha ◽  
Mahmoud Al-Sha'er ◽  
Mutasem Taha
Keyword(s):  
Acetic Acid ◽  
Type Ii Diabetes Mellitus ◽  
Biological Evaluation ◽  
Diabetic Patients ◽  
Type Ii ◽  
Design Synthesis ◽  
Multifunctional Protein ◽  
Design And Synthesis ◽  
Dpp Iv

As incidence rate of type II diabetes mellitus continues to rise, there is a growing need to identify novel therapeutic agents with improved efficacy and reduced side effects. Dipeptidyl peptidase IV (DPP IV) is a multifunctional protein involved in many physiological processes. It deactivates the natural hypoglycemic incretin hormone effect. Inhibition of this enzyme increases endogenous incretin level, incretin activity and should restore glucose homeostasis in type II diabetic patients making it an attractive target for the development of new antidiabetic drugs. One of the interesting reported anti- DPP IV hits is Gemifloxacin which is used as a lead compound for the development of new DPP IV inhibitors. In the current work, design and synthesis of a series of N4-sulfonamido-succinamic, phthalamic, acrylic and benzoyl acetic acid derivatives was carried out. The synthesized compounds were evaluated for their in vitro anti-DPP IV activity. Some of them have shown reasonable bioactivity, where the most active one 17 was found to have an IC50 of 33.5 μM.

scholarly journals Competitive Inhibitors ofHelicobacter pylori Type II Dehydroquinase: Synthesis, Biological Evaluation, and NMR Studies

ChemMedChem ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. 756-770 ◽  
Author(s):  
Cristina Sánchez-Sixto ◽  
Verónica F. V. Prazeres ◽  
Luis Castedo ◽  
Se Won Suh ◽  
Heather Lamb ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Type Ii ◽  
Nmr Studies ◽  
Competitive Inhibitors ◽  
Type Ii Dehydroquinase

The crystal structure of a type II dehydroquinase fromMycobacterium tuberculosis

1996 ◽  
Vol 52 (a1) ◽  
pp. C115-C115
Author(s):  
D. G. Gourley ◽  
J. R. Coggins ◽  
A. R. Hawkins ◽  
N. W. Isaacs
Keyword(s):  
Crystal Structure ◽  
Type Ii ◽  
Type Ii Dehydroquinase

Crystallization and preliminary X-ray crystallographic analysis of type II dehydroquinase fromHelicobacter pylori

2001 ◽  
Vol 57 (2) ◽  
pp. 279-280 ◽  
Author(s):  
Jae Eun Kwak ◽  
Jae Young Lee ◽  
Byung Woo Han ◽  
Jinho Moon ◽  
Se Hui Sohn ◽  
...  
Keyword(s):  
Crystallographic Analysis ◽  
Type Ii ◽  
X Ray ◽  
Type Ii Dehydroquinase

scholarly journals Cloning, sequencing, expression, purification and preliminary characterization of a type II dehydroquinase from Helicobacter pylori

1996 ◽  
Vol 319 (2) ◽  
pp. 559-565 ◽  
Author(s):  
Joanna R BOTTOMLEY ◽  
Christopher L. CLAYTON ◽  
Peter A. CHALK ◽  
Colin KLEANTHOUS
Keyword(s):  
Helicobacter Pylori ◽  
Sequence Data ◽  
Shikimate Pathway ◽  
Cosmid Library ◽  
Type Ii ◽  
Gene Encoding ◽  
Heat Stable ◽  
Plasmid Construct ◽  
H Pylori ◽  
Type Ii Dehydroquinase

A heat-stable dehydroquinase was purified to near homogeneity from a plate-grown suspension of the Gram-negative stomach pathogen Helicobacter pylori, and shown from both its subunit and native molecular masses to be a member of the type II family of dehydroquinases. This was confirmed by N-terminal amino acid sequence data. The gene encoding this activity was isolated following initial identification, by random sequencing of the H. pylori genome, of a 96 bp fragment, the translated sequence of which showed strong identity to a C-terminal region of other type II enzymes. Southern blot analysis of a cosmid library identified several potential clones, one of which complemented an Escherichia coliaroD point mutant strain deficient in host dehydroquinase. The gene encoding the H. pylori type II dehydroquinase (designated aroQ) was sequenced. The translated sequence was identical to the N-terminal sequence obtained directly from the purified protein, and showed strong identity to other members of the type II family of dehydroquinases. The enzyme was readily expressed in E. coli from a plasmid construct from which several milligrams of protein could be isolated, and the molecular mass of the protein was confirmed by electrospray MS. The aroQ gene in H. pylori may function in the central biosynthetic shikimate pathway of this bacterium, thus opening the way for the construction of attenuated strains as potential vaccines as well as offering a new target for selective enzyme inhibition.

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