Academic Journal

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

Bibliographic Details
Title: New inhibitors of Helicobacter pylori urease holoenzyme selected from phage-displayed peptide libraries.
Authors: Houimel, M., Mach, J.P., Corthésy-Theulaz, I., Corthésy, B., Fisch, I.
Publication Year: 1999
Collection: Université de Lausanne (UNIL): Serval - Serveur académique lausannois
Subject Terms: 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
Description: 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.
Document Type: article in journal/newspaper
Language: English
ISSN: 0014-2956
Relation: European Journal of Biochemistry; https://iris.unil.ch/handle/iris/93389; serval:BIB_58AEAED6EF58; 000081104900019
DOI: 10.1046/j.1432-1327.1999.00430.x
Availability: https://iris.unil.ch/handle/iris/93389
https://doi.org/10.1046/j.1432-1327.1999.00430.x
Accession Number: edsbas.EE8444E
Database: BASE
Description
ISSN:00142956
DOI:10.1046/j.1432-1327.1999.00430.x