Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme
Paradis-Bleau , Catherine, Beaumont, Mélanie , Boudreault, Lydia , Lloyd, Adrian, Sanschagrina, François , Bugg, Timothy D. H. and Levesquea, Roger C. . (2006) Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme. Peptides, Volume 27 (Number 7). pp. 1693-1700. ISSN 0196-9781Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.peptides.2006.01.017
The purified Pseudomonas aeruginosa cell wall biosynthesis MurD amide ligase enzyme was used to screen C-7-C and 12 mers peptides from phage display libraries using competitive biopanning approaches with the specific substrates D-glutamate and ATP. From the 60 phage-encoded peptides identified, DNA was sequenced, deduced amino acid sequences aligned and two peptides were synthesized from consensus sequences identified. The UDPN-acetylmuramyl-L-alanine MurD substrate was synthesized, purified and used to develop a spectrophotometric assay. One peptide synthesized was found to specifically inhibit ATPase activity of MurD. The IC50 value was estimated at 4 mu M for the C-7-C MurDp1 peptide. The loop conformation of MurDp1 was shown to be important for the inhibition of the UDP-N-acetylmuramyl-L-alanine:D-glutamate MurD ligase. The linear 12 mers MurD2 peptide has an IC50 value of 15 mM. A conserved amino acid motif was found between MurDp2 and the bacterial glyceraldehyde 3-phosphate dehydrogenase indicating that MurDp2 binds at a protein-protein interacting site. The approach proposed and results obtained suggest that efficient peptide inhibitors as well as protein-protein interaction domains can be identified by phage display. (c) 2006 Elsevier Inc. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
|Divisions:||Faculty of Science > Chemistry|
|Journal or Publication Title:||Peptides|
|Official Date:||March 2006|
|Number of Pages:||8|
|Page Range:||pp. 1693-1700|
|Access rights to Published version:||Restricted or Subscription Access|
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