New inhibitors of Helicobacter pylori urease holoenzyme selected from phage-displayed peptide libraries.

Details

Serval ID
serval:BIB_58AEAED6EF58
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
New inhibitors of Helicobacter pylori urease holoenzyme selected from phage-displayed peptide libraries.
Journal
European Journal of Biochemistry
Author(s)
Houimel M., Mach J.P., Corthésy-Theulaz I., Corthésy B., Fisch I.
ISSN
0014-2956 (Print)
ISSN-L
0014-2956
Publication state
Published
Issued date
1999
Volume
262
Number
3
Pages
774-780
Language
english
Abstract
Urease is an important virulence factor for Helicobacter pylori and is critical for bacterial colonization of the human gastric mucosa. Specific inhibition of urease activity has been proposed as a possible strategy to fight this bacteria which infects billions of individual throughout the world and can lead to severe pathological conditions in a limited number of cases. We have selected peptides which specifically bind and inhibit H. pylori urease from libraries of random peptides displayed on filamentous phage in the context of pIII coat protein. Screening of a highly diverse 25-mer combinatorial library and two newly constructed random 6-mer peptide libraries on solid phase H. pylori urease holoenzyme allowed the identification of two peptides, 24-mer TFLPQPRCSALLRYLSEDGVIVPS and 6-mer YDFYWW that can bind and inhibit the activity of urease purified from H. pylori. These two peptides were chemically synthesized and their inhibition constants (Ki) were found to be 47 microM for the 24-mer and 30 microM for the 6-mer peptide. Both peptides specifically inhibited the activity of H. pylori urease but not that of Bacillus pasteurii.
Keywords
Amino Acid Sequence, Bacterial Proteins/antagonists & inhibitors, Bacterial Proteins/isolation & purification, Bacteriophage M13/genetics, Base Sequence, Enzyme Inhibitors/pharmacology, Helicobacter pylori/chemistry, Helicobacter pylori/enzymology, Holoenzymes/metabolism, Kinetics, Molecular Sequence Data, Peptide Library, Peptides/genetics, Peptides/pharmacology, Protein Binding, Substrate Specificity, Urease/antagonists & inhibitors, Urease/isolation & purification
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:53
Last modification date
20/08/2019 14:12
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