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Multivariate design...
Multivariate design, synthesis, and biological evaluation of peptide inhibitors of FimC/FimH protein-protein interactions in uropathogenic Escherichia coli
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- Larsson, Andreas (författare)
- Umeå universitet,Kemiska institutionen
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- Johansson, Susanne M. C. (författare)
- Umeå universitet,Kemiska institutionen
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Pinkner, Jerome S. (författare)
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Hultgren, Scott J. (författare)
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- Almqvist, Fredrik (författare)
- Umeå universitet,Kemiska institutionen
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- Kihlberg, Jan (författare)
- Umeå universitet,Kemiska institutionen
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- Linusson, Anna (författare)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
- 2005-02-01
- 2005
- Engelska.
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 48:4, s. 935-945
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- A peptide library targeting protein-protein interactions crucial for pilus assembly in Gram negative bacteria has been designed using statistical molecular design. A nonamer peptide scaffold was used, with seven positions being varied. The selection was performed in the building block space, and previously known structure-activity data were included in the design procedure. This resulted in a heavily reduced library consisting of 32 peptides which was prepared by solid-phase synthesis. The ability of the peptides to inhibit the protein-protein interaction between the periplasmic chaperone FimC and the pilus adhesin FimH was then determined in an ELISA. Novel peptides with the capability to inhibit the FimC/FimH protein(-)protein interaction to the same extent as the native FimC peptides were discovered. Multivariate QSAR studies of the response in the ELISA gave valuable information on the properties of amino acids which were preferred at the seven positions in the nonamer scaffold. This information can be used in attempts to develop optimized peptides and peptidomimetics that inhibit pilus assembly in pathogenic bacteria.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
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- art (ämneskategori)
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