Open AccessNew inhibitors of Helicobacter pylori urease holoenzyme selected from phage‐displayed peptide libraries
Author(s) -
Houimel Mehdi,
Mach JeanPierre,
CorthésyTheulaz Irène,
Corthésy Blaise,
Fisch Igor
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00430.x
Subject(s) - urease , helicobacter pylori , peptide , peptide library , phage display , context (archaeology) , microbiology and biotechnology , bacteria , chemistry , enzyme , biochemistry , biology , peptide sequence , gene , paleontology , genetics
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 ( K i ) were found to be 47 µ m for the 24‐mer and 30 µ m for the 6‐mer peptide. Both peptides specifically inhibited the activity of H. pylori urease but not that of Bacillus pasteurii .