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Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme
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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 0196-9781
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Official URL: http://dx.doi.org/10.1016/j.peptides.2006.01.017
Abstract
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 | ||||||||||
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| Subjects: | Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
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| Divisions: | Faculty of Science > Chemistry | ||||||||||
| Journal or Publication Title: | Peptides | ||||||||||
| Publisher: | Elsevier Inc | ||||||||||
| ISSN: | 0196-9781 | ||||||||||
| Official Date: | March 2006 | ||||||||||
| Dates: |
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| Volume: | Volume 27 | ||||||||||
| Number: | Number 7 | ||||||||||
| Number of Pages: | 8 | ||||||||||
| Page Range: | pp. 1693-1700 | ||||||||||
| Identification Number: | 10.1016/j.peptides.2006.01.017 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||
| URI: | http://wrap.warwick.ac.uk/id/eprint/33330 |
Data sourced from Thomson Reuters' Web of Knowledge
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