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New inhibitors of Helicobacter pylori urease holoenzyme selected from phage-displayed peptide libraries
- Source :
- European Journal of Biochemistry. 262:774-780
- Publication Year :
- 1999
- Publisher :
- Wiley, 1999.
-
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.
- Subjects :
- Phage display
Urease
Molecular Sequence Data
Peptide
Context (language use)
Biology
Biochemistry
Virulence factor
Substrate Specificity
Microbiology
Bacterial Proteins
Peptide Library
Amino Acid Sequence
Enzyme Inhibitors
Peptide library
Peptide sequence
chemistry.chemical_classification
Base Sequence
Helicobacter pylori
biology.organism_classification
Kinetics
chemistry
biology.protein
Holoenzymes
Peptides
Bacteriophage M13
Protein Binding
Subjects
Details
- ISSN :
- 14321033 and 00142956
- Volume :
- 262
- Database :
- OpenAIRE
- Journal :
- European Journal of Biochemistry
- Accession number :
- edsair.doi.dedup.....3a59bc5d001709c31eece39bee509578